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Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with limited treatment options. This study explores the potential of novel 5-nitro-thiophene-thiosemicarbazone derivatives as therapeutic agents for PDAC. We evaluated the cytotoxicity of seven derivatives in peripheral blood mononuclear cells (PBMCs) and PDAC cell lines. Promising candidates (PR12 and PR17) were further analyzed for their effects on colony formation, cell cycle progression, and reactive oxygen species (ROS) production. PR17, the most promising derivative, was subjected to additional investigation, including analysis of autophagy-related genes and protein kinase inhibition. Three derivatives (PR16, PR19, and PR20) displayed cytotoxicity towards PBMCs. PR12 reduced colony formation and G0/G1 cell cycle arrest in PDAC cells. Notably, PR17 exhibited potent activity in MIA PaCa-2 cells, inducing S-phase cell cycle arrest, downregulating autophagy genes, and inhibiting key protein kinases. PR17, a 5-nitro-thiophene-thiosemicarbazone derivative, demonstrates promising antineoplastic activity against PDAC cells by potentially modulating cell cycle progression, autophagy, and protein kinase signaling. Further studies are warranted to elucidate the detailed mechanism of action and explore its efficacy in vivo. [Display omitted] • Three out of 7 nitrothiophene-thiosemicarbazone derivatives (PR-16, PR-19, and PR-20) were toxic to PBMCs. • The PR-12, PR-13, and PR-17 derivatives demonstrated cytotoxicity against PDAC cell lines. • PR-17 derivative has induced cell arrest in the S phase and increased the percentage of Mia Paca-2 cells in the Sub-G0 phase. • Treatment with PR-17 increases superoxide production and decreased caspase-7, SOD1, ATG5, and LC3 gene expression. • Interference caused by PR-17 in the MIA PaCa-2 cell line led to the deactivation of phosphorylated kinases. [ABSTRACT FROM AUTHOR]

• Novel 3APHT successfully characterized using spectroscopy integrated DFT/TD-DFT. • Calculated through PED showed that 3APHT contains 96 types of vibrations. • 3APHT has chemically inert molecular structure with low polarizability. • 3APHT selective and sensitive towards Cu2+ ions. • 3APHT acts as an inhibitor for the overexpressed receptor of breast cancer caused by Cu pollution. A novel thiosemicarbazone scaffold, namely 3-acetylpyridine-2-hydroxyphenyl thiosemicarbazone (3APHT), which contains π-conjugated heterocyclic and phenyl rings, was successfully synthesized and characterized experimentally and theoretically. Through TD/DFT calculations, it was found that the new compound has 14 signals in 13CNMR spectroscopy, 96 types of vibrations for vibration analysis, and n- π* and π-π* electronic transitions that lead to an 87.12 % HOMO-LUMO excitation. The vibrations follow 3N-6 degrees of freedom for a non-linear compound. Based on the global reactivity parameter and other results, it has been shown that 3APHT has potential applications in metal ion detection and as an inhibitor for the overexpressed receptor of breast cancer caused by copper ions pollution. The novel APHT was optimized as a colorimetric metal ions recognition using UV–Vis analysis. Suitable conditions for 3APHT to act as a colorimetric metal ion recognition was detected in DMSO/water (8:2 v/v, pH 7). The change of test strips from colorless to yellowish revealed the presence of Cu2+ ions in the water. The selectivity toward the Cu2+ ion did not interfere with other metal ions. The potential of 3APHT to inhibit the upregulation of apoptotic genes caused by copper ions in BCL-2 family proteins—the main cause of breast cancer—was determined using an in-silico approach. The results showed strong binding of 3APHT with BCL-2, BCL-W, MCL-1, and ER-α through hydrogen bonds and electrostatic interactions at -6.35, -6.31, -8.05, and -7.05 kcal/mol, respectively. The physicochemical through ADME analysis showed that the compound has a structure that presents good absorption properties, therefore permeability across the cell membrane, and good theoretical oral bioavailability. [Display omitted] [ABSTRACT FROM AUTHOR]

• Imine group-containing compounds and coordination compounds with imine ligands, focusing on thiosemicarbazones, Schiff bases, hydrazones, and benzopyrazines as potential Chagas disease drugs, were reviewed. • The literature evaluation about the coordination compounds unveils that vanadium-containing coordination compounds and ferrocenyl organometallic compounds are promising due to their strong activity against Chagas disease. • Schiff bases derived from diaminomaleonitrile show remarkable antichagasic inhibitory activity. • Molecular docking and DFT studies provided insights into the interactions of compounds within the hydrophobic pocket of Cruzain. In this work, compounds containing imine groups, as well as coordination compounds with this type of ligand, evaluated as potential Chagas disease drugs, published in the last ten years, were reviewed and discussed. Four classes of organic compounds were found: thio and semicarbazones, Schiff bases, hydrazones and benzopyrazines. ADMET parameters were calculated for organic molecules using Molinspiration Chemoinformatics and ProTox-II softwares. Coordination compounds containing Vanadium (IV or V) and organometallic ferrocenyl or cyrhetrenyl portions stand out the most in activity due to the promising in vitro results. Relationships between in silico activity and physicochemical properties were discussed by the analyses of color-filling graphs. Molecular docking studies suggested that interactions are more abundant in the hydrophobic pocket through residues Gly66, Leu67, Met68, and DFT, which have shown higher electron-receptor capacity of charge-transfer complexes (CTC) on the diaminomaleonitrile-derived Schiff bases. [Display omitted] [ABSTRACT FROM AUTHOR]

• Two thiosemicarbazone-based Cu complexes with proapoptotic activity were synthesized. • Complex 1 bound to DNA via an intercalation mode and arrested cell cycle in S phase. • Complex 1 enhanced ROS generation, caused mitochondria dysfunction and ATP depletion. The copper ion and thiosemicarbazone group are well known for their biological activity, endowing the thiosemicarbazone copper complexes with medicinal perspectives. In this work, two copper complexes [Cu(qcpt)(PPh 3) 2 Br]·2CH 3 CN (1) and [Cu 2 (qcapt)(Ac) 2 (CH 3 O)] (2) derived from the bioactive quinoline-thiosemicarbazone conjugate (qcpt = quinoline-2- carboxaldehyde-4-pyridine-3-thiosemicarbazone; qcapt = quinoline-2-carboxaldehyde acid-4- pyridine-3-thiosemicarbazone) were rationally synthesized and characterized by single crystal X-ray diffraction, Infrared (IR) spectroscopy, X-ray photoelectron spectroscopy (XPS), and etc. In vitro antitumor studies suggested that complexes 1 and 2 showed effective anti-proliferative activity against malignant tumor cells, especially for complex 1 that exhibited the most sensitive against SMMC7721 cells (human liver carcinoma cell lines). Further, mechanistic studies showed that complex 1 could readily enter the cells, block the cell cycle, cause mitochondrial dysfunction and ATP depletion, enhance the levels of intracellular reactive oxygen species (ROS), and eventually trigger cell death via apoptosis. Additionally, complex 1 bound to CT-DNA via an intercalation mode as evidenced by spectroscopic experiments, molecular docking study and cleaved pBR322 DNA efficiently in the presence of H 2 O 2. Copper complex 1 demonstrated most sensitive against SMMC7721 cells. The mechanistic studies elucidated that complex 1 could enter the cells, arrest the cell cycle, elicit ROS overproduction and cause mitochondrial dysfunction accompanied with ATP depletion. Eventually, complex 1 triggered apoptotic tumor cell death. [Display omitted] [ABSTRACT FROM AUTHOR]

• Coordination chemistry of thiosemicarbazide and its non-Schiff base derivatives. • Summary of development in TSC ligands over the 90 years since the first complexes. • Different possibilities of thiosemicarbazide modification. • Structural properties and synthesis of complexes with non-Schiff base ligands. • Structural variety, biological and physicochemical properties of TSC complexes. Very rich coordination chemistry of thiosemicarbazide based ligands is mainly associated with the diversity of their Schiff base derivatives, known as thiosemicarbazones. The significant interest in thiosemicarbazones and their metal complexes arises from a wide range of valuable biological, chemical and physico-chemical features, as documented by numerous review papers in medicinal, structural, analytical chemistry, catalysis and other. The thiosemicarbazide based ligands other than Schiff bases did not draw the same attention. A literature survey, however, shows considerable number of non-Schiff base derivatives with interesting coordination chemistry, giving rise to metal complexes with pronounced structural diversity and useful properties. Considering the polydentate thiosemicarbazide scaffold [N–N–C(=S)–N] it is not surprising that its other derivatives can offer versatile coordination modes and stable complexes with variety of metal ions. This article attempts to bring together the thiosemicarbazide derived ligands other than Schiff bases, and to explore their coordination tendencies as well as the structural aspects of their metal complexes. The first papers in coordination chemistry of thiosemicarbazide were reported exactly 90 years ago. Therefore, it is also our aim to gain better overview of various types of thiosemicarbazide ligands that have emerged since, and to understand different possibilities of thiosemicarbazide modification. In order to present and compare the molecular and supramolecular properties the review primary relies on structurally characterized coordination compounds. It also includes some experimental charge density findings in an effort to explain behaviour of thiosemicarbazide ligands at subatomic level. [Display omitted] [ABSTRACT FROM AUTHOR]

• Pd(II) and Pt(II) complexes with coumarin-thiosemicarbazone ligands were prepared. • Triphenylphosphine was included as lipophilic and stabilizing ligand. • Moderate activity against T. cruzi appeared because of palladium complexation. • Selected palladium compound diminished the infection rate of Vero cells with T. cruzi. • Compounds were able to produce ROS and mitochondrial dysfunction in the parasites. Chagas disease is a neglected tropical disease caused by the parasite Trypanosoma cruzi. The disease is endemic in 21 Latin American countries, but it has also been found worldwide. Current treatments for Chagas disease are not effective in all stages of the disease and can have severe side effects. In recent years, there has been a growing interest in the development of new drugs for the treatment of Chagas disease, including metal complexes containing bioactive ligands. In this work, we designed and synthesized eight novel palladium and platinum complexes of the formula [M(L)(PPh 3)] containing four different coumarin-thiosemicarbazone hybrid ligands (H 2 L) as bioactive ligands and triphenylphosphine as lipophilic co-ligand. Compounds were characterized in the solid state and in solution including the resolution of the crystal structure of two of them by single crystal X-ray diffraction. The activity of these hybrids and their corresponding complexes against T. cruzi , along with their unspecific cytotoxicity, was assessed. The results showed that the palladium complexes fairly improved the ligands' anti- T. cruzi activity in vitro but also the cytotoxicity on some mammalian cell lines. The most active palladium compound decreased the rate of parasitic infection of Vero cells. Synergy studies with benznidazole were also performed for this compound. In addition, we explored mitochondrion disruption and ROS generation as potential modes of action for the obtained compounds. Further studies are needed to optimize the design of new compounds to attain less unspecific toxicity and higher anti T. cruzi activity. [Display omitted] [ABSTRACT FROM AUTHOR]

• Novel bis -Schiff base ligand and Ni(II) complex based on bis (thiosemicarbazone). • Elucidation of crystal structures of nickel(II) linkage isomers by XRD studies. • Cytotoxicity assessment of both ligand and Ni(II) complex against MCF-7 cell lines. • DFT computational investigations on the structural stability of the linkage isomers. • Molecular docking simulation on the interaction of ligand and complex with DNA. The synthesis of a new nickel(II) coordination complex bearing acenaphthenequinone bis (thiosemicarbazone), [NiL] , a N 2 S 2 tetradentate bis -Schiff base ligand (H 2 L), under reflux and sonochemical conditions is reported. These new compounds (H 2 L and [NiL]) have been characterized by using various techniques such as FT-IR, 1H NMR, ESI-Mass spectrometry, UV–Vis, TGA, and elemental analysis. In addition, molecular structure of the ligand, (H 2 L) 2 .4DMSO.H 2 O, and complexes [NiL] 3 .2.5CH 3 OH.0·5H 2 O (1) and [NiL] .CH 3 CN (2) have been determined by single crystal X-ray diffraction studies. The molecular structures of the nickel(II) complexes (1 and 2) revealed that they are structural isomers differing in their chelate ring arrangements (symmetric 5–5–5-trichelate system for 1 and asymmetric 4–6–5-trichelation for 2). In addition, the anticancer activity of H 2 L and its nickel(II) complex, [NiL] , have been evaluated against human breast cancer cell line (MCF-7) using colorimetric 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The cytotoxicity of both compounds was compared with two standard anticancer drugs, cisplatin and oxaliplatin. Density functional theory (DFT) calculations were done to predict the chemical reactivity of H 2 L and complexes 1 and 2. Furthermore, DNA binding with H 2 L and [NiL] was performed using docking simulation to reveal that acenaphthenequinone and amine groups in thiosemicarbazone moieties in both ligand and complex are responsible for the groove binding to DNA via the formation of hydrogen, pi-anion, and pi-sigma bonds. [Display omitted] [ABSTRACT FROM AUTHOR]

• Two antimony complexes with tridentate N 2 S thiosemicarbazones were prepared. • The complexes, in comparison to the ligands and ampicillin, displayed elevated inhibitions in staphylococcus aureus and escherichia coli strains. • The complexes, comparing with the ligands, exhibited higher cytotoxicity towards MCF-7 cells. • This cytotoxicity towards MCF-7 cells is less comparing with that of doxorubicin, but doxorubicin is much more toxic towards normal BHK cells. Addition of antimony(III) chloride to ligands { HL1 = 4-(4-nitrophenyl)-1-((pyridin-2-yl)methylene)thiosemicarbazide and HL2 = 4-(2-methoxyphenyl)-1-((pyridin-2-yl)methylene)thiosemicarbazide} produced the complexes [Sb(L1)Cl 2 ] (C1) and [Sb(L2)Cl 2 ] (C2), respectively. These complexes were formulated based on elemental, spectroscopic and solution conductivity data. X-ray crystallography elucidated the packing of C2 in the triclinic P-1 space group and the exhibition of pseudo octahedral geometry around the antimony cation. The complexes (20 mg/ml) showed the largest inhibition zones in Staphylococcus aureus (34 mm for C1 and 36 mm for C2) and Escherichia coli (33 mm for C1 and 36 mm for C2) strains. HL1 showed no inhibition in the bacterial strains and HL2 inhibited the strains of Staphylococcus aureus and E. coli at 11 and 10 mm, while ampicillin inhibited these strains at 21 and 25 mm, respectively. The ligands' cytotoxic effects were investigated on four human cancer cells and the greatest effect was on the breast MCF-7 cells. The compounds HL1, HL2, C1, C2 and doxorubicin revealed cytotoxicity with IC 50 values of 52.4 ± 0.38, 153.7 ± 1.05, 37.5 ± 0.32, 21.8 ± 0.20 and 9.66±0.25 μM in the MCF-7 cancer cells and of 54.8 ± 0.85, 82.7 ± 0.44, 176.5 ± 0.70, 196.7 ± 1.16 and 36.42±0.08 μM in normal baby hamster kidney (BHK) cells. [ABSTRACT FROM AUTHOR]

Copper complexes have shown promising anticancer properties, but they are often poorly soluble in aqueous solutions, thus limiting their possible medical developments and applications. We have recently isolated some copper(II) complexes with salicylaldehyde thiosemicarbazone ligands exhibiting remarkable nanomolar cytotoxic activity, but in vivo tests evidenced several difficulties related to their poor solubility. To overcome these limitations and increase solubility in aqueous solution, herein we report the synthetic strategy that led to the introduction of the sulfonic group on the ligands, then separated as salts (NaH 2 L 1 - NaH 2 L 5 ), as well as the synthesis and characterization of the related copper(II) complexes. The characterization of the complexes is completed by the analysis of the structures obtained by X-rays diffraction on single crystals on the species [Cu(HL5)(H 2 O)] 2 .2H 2 O, [Cu(HL2)(H 2 O) 2 ].2H 2 O, and [Cu(HL1)(H 2 O] 2 .2H 2 O. While the uncoordinated ligands do not affect cancer cell viability, copper(II) complexes exhibit low to sub-micromolar cytotoxic activity, which is maintained in 3D (HCT-15 and 2008) spheroidal models of cancer cell. Notably, copper(II) complexes were selective towards cancer cells, showing high selectivity indexes. Investigations focused on elucidating the mechanism of action evidenced the protein disulfide-isomerase as an innovative molecular target for this class of water-soluble copper(II) complexes. Finally, preliminary in vivo experiments performed with the most representative derivative in the murine Lewis Lung Carcinoma, highlight its significant antitumor efficacy and better tolerability profile with respect to the reference metallodrug, suggesting for this sulfonated Cu(II) complex a potential clinical relevance. [Display omitted] • Water-soluble thiosemicarbazonic copper(II) complexes were synthetized. • Copper(II) complexes exhibit low to sub-micromolar cytotoxic activity. • Mechanistic insights revealed protein disulfide isomerase as a target. • Preliminary in vivo studies highlighted significant antitumor efficacy. [ABSTRACT FROM AUTHOR]

[Display omitted] • New thiosemicarbazone ligand derived from 4-formyl-3-hydroxy-2-naphthoic acid (H 3 L·CH 3 OH (1)) and their two Cu(II) complexes with composition [Cu(H 2 L)Cl](dmf) (2), [Cu(H 2 L)NO 3 (dmf)] (3) were synthesized and fully characterized. • Magnetic investigations of complex 2 revealed the presence of noticeable magnetic couplings between Cu(II) ions, while compound 3 shows the behavior typical of magnetically isolated Cu(II) centers. New thiosemicarbazone ligand derived from 4-formyl-3-hydroxy-2-naphthoic acid (H 3 L·CH 3 OH (1)) and their two copper(II) complexes with composition [Cu(H 2 L)Cl] 2 .2(dmf) (2), [Cu(H 2 L)NO 3 (dmf)] (3) were synthesized and characterized by thermal analysis, IR-, EPR- spectroscopy and single X-ray diffraction method. In both complexes the mono-deprotonated ligand coordinate tridentate to Cu(II) ion by ONS donor atoms provided by phenolic oxygen, azomethine nitrogen and thiol sulfur. In 2 binuclear complex has the square–planar environment of one copper(II) completed by Cl- anion, while a tetragonal pyramid of other metal is formed by Cl- anion and S atom from the neighboring organic ligand. The copper ion in the mononuclear complex 3 adopt a square-pyramidal structure, where the coordination number of copper(II) ion is adjusted to 5 by O atoms of NO 3 − anion and dimethylformamide molecule. Magnetic investigations of complex 2 revealed the presence of noticeable magnetic couplings between Cu(II) ions, while compound 3 shows the behavior typical of magnetically isolated Cu(II) centers. The compounds tested against St. aureus, C. albicans, E. coli and Kl. Pneumonia were found to be more active against gram-positive bacteria strains. [ABSTRACT FROM AUTHOR]

[Display omitted] • Mixed ligand metal complexes with isatine-thiosemicarbazones and Cu(II)/Cd(II)/Fe(III) was synthesized. • Fe-complex showed the highest antibacterial and anticancer activity. • Cu-complex exhibited the best photodegradation efficiency for rose bengal dye. Metal complexes with thiosemicarbazones and isatine have been shown to exhibit a wide range of biological activities, including antibacterial, antifungal, and anticancer activity. These complexes have also been shown to be effective photocatalysts for degrading dyes, making them a subject of significant interest. This article presents the synthesis and characterization of mixed ligand complexes of isatine-thiosemicarbazones to explore their biological activity and potential for photocatalytic applications. In this study, we synthesized mixed ligand complexes of isatine-thiosemicarbazones with various metal ions, including Cu(II), Cd(II), and Fe(III). Characterization techniques such as elemental analysis, infrared (IR), mass spectrometry (MS), thermogravimetric analysis (TGA), and scanning electron microscope (SEM) were utilized to understand their structural composition and morphological properties. The complexes exhibited remarkable antibacterial activity against Escherichia coli, Staphylococcus aureus, Streptococcus mutants, and antifungal effects on Candida albicans. Notably, the Fe-complex demonstrated the highest activity, followed by the Cu-complex and Cd-complex. Strong anticancer effects were observed against human liver HepG2 and breast MDA cancer cells, with the Fe-complex displaying the highest activity. Additionally, the complexes displayed significant photocatalytic activity in the decomposition of rose bengal dye using ultraviolet light irradiation, with the Cu-complex showing the highest degradation efficiency. The results indicate that these mixed ligand metal complexes have potential therapeutic applications as antibacterial, antifungal, and anticancer agents. Moreover, they suggest their prospective utility as photocatalysts for the remediation of dye-contaminated wastewater. [ABSTRACT FROM AUTHOR]

[Display omitted] • 2-Chloroquinoline-3-carboxaldehyde-4(N)-substituted thiosemicarbazone derivate of Cu(II) complexes. • DNA/BSA binding studies for the ligands and their corresponding complexes. • In vitro studies were carried out against human kidney cell (HEK) and HeLa cells. • AO/EtBr and DAPI staining studies were carried out for the compounds. Copper(II) metallates of 2-chloroquinoline-3-carboxaldehyde-4(N)-substituted thiosemicarbazone (CuQ1, CuQ2, CuQ3, CuQ4) were synthesized, characterized by Fourier-Transform Infrared (FT-IR), Ultraviolet–Visible (UV–Vis), Electron Paramagnetic Resonance (EPR) and Mass spectrometry. The true nature of the ligands and a representative complex was confirmed by X-ray single crystal analysis. During the complexation, the ligands underwent cyclisation to form thiadiazole and two units of thiadiazole were coordinated to copper ion through N2-nitrogen atom. The remaining sites were occupied with two chloride ions and a water molecule which led to a square pyramidal geometry around copper ion. Absorption and emission titration methods confirmed the partial intercalative mode of binding interaction between CT-DNA and the metal complexes. The interaction between complexes and BSA led to the formation of ground state fluorophore-quencher complex by following static quenching mechanism. In vitro cytotoxic effect of the ligands and complexes were done by taking Human cervical cancer (HeLa) cells and toxicity of the test compounds were analyzed by using normal human kidney cell (HEK). The complexes CuQ2, CuQ3 and CuQ4 showed better cytotoxic activity against HeLa cells as compared with the standard cisplatin. Among the complexes, CuQ3 exhibited higher activity with least IC 50 value (17 µM). [ABSTRACT FROM AUTHOR]

• Various para-substituted thiosemicarbazone derivatives have been successfully synthesized. • These derivatives were subjected for their anti-diabetic potential using α-glucosidase and α-amylase assays. • Molecular docking studies have been carried out to know the interactions between the compounds and the enzymes. • The chemical nature of these product compounds were determined through DFT studies. This work describes the synthesis of para -substituted thiosemicarbazone derivatives by refluxing 4-ethoxybenzaldehyde (1) and 4-nitrobenzaldehyde (2) with thiosemicarbazide in ethanol with acetic acid catalyst. The resultant thiosemicarbazones were then treated with various phenacyl bromides to get the product compounds. 1H NMR and EI-MS spectroscopic methods were employed to confirm the structures of these derivatives and screened the compounds for their in vitro α-glucosidase and α-amylase inhibitory activities. Six compounds (4e, 3e, 3c, 3b, 4b, and 4c) exhibited highest α-glucosidase activity in the range of IC 50 values of 2.81 ± 1.92 to 16.16 ± 0.15 µM. Similar to this, five compounds (3e, 4e, 3b, 3c, and 4c) attributed excellent inhibitory activity in the range of IC 50 values from 3.12 ± 0.13 to 16.56 ± 0.17 µM against the α-amylase enzyme when compare with the standard acarbose. The density functional theory (DFT) study demonstrated the stability, bioactivity, and charge transfer of the compounds, while the molecular docking analysis has provided significant understanding of how the compounds interact with the enzymes. These findings provide prospective directions for the development of innovative therapeutic candidates to regulate postprandial glucose levels in diabetic patients. [Display omitted] [ABSTRACT FROM AUTHOR]

• A novel series of indole-based thiosemicarbazones (3a-o) was synthesized. • Characterization of (3a-o) was done by FTIR, 1HNMR, 13CNMR, single crystal X-ry and mass spectrometric analysis. • Probed for inhibition potential against prolyl specific oligopeptidase (POP). • Compound 3g was proceeded for mechanistic studies. • Molecular docking studies were performed to find the binding mode of most potent inhibitor. One of the highly expressed enzymes in the brain, prolyl specific oligopeptidase (POP), is a key target for the treatment of illnesses of the central nervous system including, autism spectrum, schizophrenia, Parkinson's, dementia, and Alzheimer's. In the current studies we report a series of indole based thiosemicarbazone as prolyl oligopeptidase (POP) inhibitors. Numerous approaches, such as Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), and mass-spectrometry (MS) procedures, were used to confirm the structures of all substances. These compounds were evaluated against POP interestingly all these tested molecules significantly inhibit POP in vitro at very low doses (5.74–25.30 µM). Compound 3g displayed the highest inhibition with IC 50 value 5.74 ± 0.27 µM. Kinetic studies of compounds, 3g, revealed concentration dependent type of inhibition with Ki value 4.31 ± 0.0012 µM. Furthermore, molecular docking was also performed to understand the binding modes of compounds, which correlates with our in vitro outcomes. [ABSTRACT FROM AUTHOR]

• A library of some novel thiosemicarbazones has been successfully synthesized. • All compounds underwent characterization using NMR and mass spectrometry. • These analogs were evaluated as α-glucosidase and α-amylase inhibitors. • DFT studies were carried out to determine the chemical nature of compounds. • Molecular docking studies were used to determine the binding interactions. A library of thiosemicarbazones derivatives have been synthesized by multi step reactions, characterized and screened for their in vitro α-amylase and α-glucosidase inhibitory actions. Among them, three compounds including 4b (IC 50 = 3.18 ± 1.72 and 2.11 ± 1.29 µM), 4a (IC 50 = 5.16 ± 1.12 and 7.23 ± 0.11 µM), and 4 g (IC 50 = 7.13 ± 1.21 and 9.53 ± 0.29 µM) are found as potential dual inhibitors of α-amylase and α-glucosidase enzymes, powerfull than the standard acarbose drug (IC 50 = 21.55 ± 1.31 and 16.65 ± 0.07 µM). In addition, compounds 4c, 4f, 4 h, 4d, and 4e indicated significant to less inhibitory potential. Molecular docking was performed to know the binding affinities and various interactions between the synthesized compounds and targeted proteins. For the docking analysis, the protein structure of α-amylase was taken from the Protein Data Bank (PDB) with the code 3BAJ, derived from Homo sapiens. Meanwhile, the protein structure of α-glucosidase was obtained from Beta vulgaris with the PDB code 3W37. The chemical nature of the product compounds was identified using the density functional theory (DFT) method, and the calculations were performed using the B3LYP/6–311++ G (d,p) method. Intramolecular interactions were explored using DFT-d3 and Reduced Density Gradient (RDG) analysis. Furthermore, the chemical nature of all the compounds was identified using TD-DFT at the CAM-B3LYP/6–311++ G (d,p) method. Among the synthesized compounds, 4a, 4b, and 4g show similar inhibition activities with targeted proteins. Similar activities have been confirmed using the TD-DFT method. The energy gap between the highest occupied molecular orbitals and lowest unoccopied was found as, 6.07, 6.08, and 6.07 eV, respectively. The similarty in energy gap indicated these compounds have similiar reactivity nature. [Display omitted] [ABSTRACT FROM AUTHOR]

• Cu2+, and Co2+ complexes of two 4 – Pyridyl thiosemicarbazone derivatives ligands symbolized by (H 3 L1), and (H 3 L2), were synthesized. • Complexes were examined utilizing different analytical, and spectroscopic techniques. • QTAIM topological analyses (RDG, and ELF) for both ligands were obtained using Multiwfn software. • Fluorescence studies for both ligands showed a direct increase in the intensity of emissions because of increasing Co2+ concentration in solution. • The investigated compounds (especially the free ligands) have good effects as antitumor, and DNA degradation agents. Two sets of Cu2+, and Co2+ complexes of two 4 – Pyridyl thiosemicarbazone derivatives ligands symbolized by (H 3 L1), and (H 3 L2), were synthesized and examined utilizing different analytical, and spectroscopic techniques such as (FT-IR, Elemental Analysis, Magnetic studies, PXRD, UV–Vis, and GCMS–). Thermal stability along with kinetic parameters of both Co2+ complexes were studied. 1H NMR technique was used to confirm the structures of both ligands. The proposed geometries of complexes were recognized by density function theory (DFT) calculations using Material software. Additionally, Quantum theory of atoms in molecules (QTAIM) topological analyses for both ligands were obtained using Multiwfn software. The cyclic voltammogram revealed that copper ions are electroactive and exhibited two reduction waves. Fluorescence studies for both ligands showed a direct increase in the intensity of emissions because of increasing Co2+ concentration in solution. Moreover, several biological evaluations were carried out for all six compounds to evaluate their potential use as biological agents, including antioxidant activity using 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging approach, anti-microbial activity against Staphylococcus aureus, Escherichia coli , and Candida albicans , DNA degradation activity, in addition to anticancer activity, along with molecular docking theoretical study against MCF-7 breast cancer cell line to determine the compounds ability to act as antitumor. It was found that the investigated compounds (especially the free ligands) have beneficial effects such as antimicrobial, antitumor, and DNA degradation agents. Furthermore, Co2+ complex (2) has the highest ABTS scavenging activity. [Display omitted] [ABSTRACT FROM AUTHOR]

In the quest for potent α-glucosidase inhibitors to combat diabetes, a series of novel thiosemicarbazide-based β-carboline derivatives (CTL1∼36) were synthesized and evaluated. CTL1∼36 exhibited remarkable inhibitory effects against α-glucosidase, with IC 50 values ranging from 2.81 to 12.40 μM, significantly surpassing the positive control acarbose (IC 50 = 564.28 μM). Notably, CTL26 demonstrated the most potent inhibition (IC 50 = 2.81 μM) and was characterized as a non-competitive inhibitor. Through a combination assay with fluorescence quenching, 3D fluorescence spectra, CD spectra, and molecular docking, we elucidated that CTL26 formed a complex with α-glucosidase via hydrogen bondings and hydrophobic interactions, leading to α-glucosidase conformation changes that impaired enzymatic activity. In vivo studies revealed that oral administration of CTL26 (25 and 50 mg/kg/d) reduced fasting blood glucose levels, enhanced glucose tolerance, and ameliorated lipid abnormalities in diabetic mice. These findings positioned CTL26 as a promising candidate for the development of α-glucosidase inhibitors with anti-diabetic potential. [Display omitted] • Thirty-six novel thiosemicarbazide-based β-carboline derivatives were synthesized. • All compounds showed potential α-glucosidase inhibitory activity. • The inhibition mechanism of CTL26 was investigated by multispectral methods. • CTL26 presented i n vivo hypoglycemic activity in STZ-induced diabetic mice. [ABSTRACT FROM AUTHOR]

[Display omitted] • New mono and dinuclear half-sandwiched organoruthenium(II) complexes were synthesized and characterized. • DFT studies were carried out to predict the localization of HOMO and LUMO electron densities on the complexes. • Preliminary in vitro DNA/BSA binding interaction studies of the complexes 1 & 2 was also carried out by various biophysical methods. • In vitro cytotoxic results revealed the promising and specific antitumor activity of dinuclear organoruthenium(II) complex against MDA-MB-468 cancer cell line. The present work describes the syntheses and structural characterization of new half sandwiched mono (complex 1) and dinuclear (complex 2) organoruthenium complexes derived from thiosemicarbazone ligand (L1). The molecular structures of compounds were characterized by analytical and multispectroscopic methods which corroborate well with single crystal XRD studies. DFT and TD-DFT studies of compounds revealed that HOMO electron density in L1 is localised on the thiosemicarbazide moiety while the LUMO electron density is evenly distributed over the ligand. However, in complex 1 , the HOMO and LUMO is localised on the arene moiety and partially distributed over metal ion while HOMO and LUMO in complex 2 is equally delocalised throughout the complex. The collaborative preliminary DNA binding studies revealed that complexes 1 and 2 exhibited intercalative mode of interaction. The magnitude of DNA binding strength was determined by calculating K b , K and Ksv values which demonstrated higher DNA binding propensity of complex 2. Furthermore, HSA binding studies of complexes also revealed better binding efficiency of dinuclear complex in contrast to mononuclear complex. The cytotoxic potential of dinuclear complex 2 was examined against triple negative breast cancer cell lines (MDA-MB-468 and MDA-MB-231) via MTT assay. [ABSTRACT FROM AUTHOR]

[Display omitted] • A 8HQ thiosemicarbazone fluoroscence probe for detection of Gd3+ ion is developed. • The Gd-hqtcsc acts as ON and OFF fluorescence sensor for H 2 PO 4 − and CN−, respectively. • Prominent color change with the anions can make it usuable as a naked-eye sensor. • Photopysical properties of solid Gd(III)-hqtcsc probe are explored. • Structure, bonding, spectral properties and sensor mechanisms are explained by DFT. Sensing ions by colorimetric and fluorimetric methods has grown tremendously due to the great environmental concern. This paper reports the colorimetric and fluorescent studies of cation and anion sensing by two thiosemicarbazone-supported receptors: (E)-2-((8-hydroxyquinolin-2-yl)methylene) hydrazine-1-carbothioamide (H 2 qctsc) (1) and [Gd(Hqctsc) 2 ]+ complex (2). Under irradiation at λ ex = 346 nm, the fluorescence sensing behavior of H 2 qctsc was investigated towards various metal ions (Na+, K+, Co2+, Cu2+, Cd2+, Cr3+, Fe2+, Fe3+, Al3+, Mn2+, Pb2+, Hg2+, Ni2+, Zn2+, Nd3+, Eu3+, Gd3+, Tb3+, Ho3+and Er3+) in DMSO medium. The chemosensor H 2 qctsc displayed a "Turn–Off" selective recognition towards Gd3+ ions through a 3.5-fold fluorescence quenching at 476 nm with the detection limit as low as 1.42 μM. It binds with Gd3+ in a 2:1 stoichiometric ratio. Further, the (1)-Gd3+ ensemble (2) exhibited a highly selective colorimetric and fluorimetric sensing for the biologically essential anions H 2 PO 4 − and CN− detecting the ions with a detection limit of 0.94 μM and 2.19 μM respectively, amongst a wide range of anions chosen. Colorimetric is a valuable technique since visual detection can give immediate qualitative information. In the present case, a naked eye color detection, i.e., yellow → colorless (H 2 PO 4 −) and yellow → red (CN−) by the ensemble, can add value to the sensor's employability in various fields. The coordination behavior of H 2 qctsc was examined in a highly aqueous medium (9:1 H 2 O: DMSO) by adopting the potentiometric and spectrophotometric methods, which revealed the formation of a very stable complex with a high formation constant (logβ = 24.75), demonstrating it as a potent chelator for Gd3+ ion. The stoichiometry of the complex was determined by Job's plot method, which confirmed the ML 2 -type complex. Additionally, a solid complex 2′ abbreviated as [Gd(Hqctsc)(qctsc)] was synthesized using the conventional method and was characterized by advanced spectroscopic techniques. The spectral studies of the synthesized complex further establish its high selective recognition towards H 2 PO 4 − and CN− ions. Density functional theory (DFT) studies confirmed the structure, bonding, spectra, and sensing mechanism of H 2 qctsc and the Gd-complex. [ABSTRACT FROM AUTHOR]

• Novel thiosemicarbazones synthesized from carbonyl compounds and thiosemicarbazide. • Compounds characterized using UV-Vis and FT-IR spectral techniques. • Demonstrated potent antibacterial activity against Bacillus subtilis and Escherichia coli. • Exhibited significant antidiabetic activity, surpassing acarbose in molecular docking. • Promising candidates WS-1 and WS-2 showed lowest binding energies with Alpha-glucosidase. Thiosemicarbazones and their derivatives were synthesized by reacting carbonyl compounds with thiosemicarbazide, followed by treatment with metal salts. The prepared thisemicarbazones such as (2E)-2-[(1,5,7-trichloronaphthalen-2-yl)-methylidene]-hydrazine-1-carbothioamide, (2 E)-2-[(1,5,7-trihydroxynaphthalen-2-yl)-methylidene]hydrazine-1-carbothioamide and these were characterized by using diverse spectral techniques, such as UV–Vis and FT-IR. The synthesized compounds were subsequently evaluated for their antibacterial properties against Gram(+) Bacillus subtilis and Gram(-) Escherichia coli , using ciprofloxacin as a reference, as well as for their anti-microbial activities. For the evaluation of anti-diabetic activity, Acarbose served as the reference. Molecular docking results indicated that WS-1 and WS-2 exhibited superior performance against Alpha-glucosidase proteins, evidenced by their lowest binding energies (−8.1 and −8.3 kcal/mol) respectively compared to other ligands. These findings suggest that WS-1 and WS-2 are promising candidates for further research and development by pharmaceutical companies to explore additional biological activities. [Display omitted] [ABSTRACT FROM AUTHOR]

• 2D/ 3D QSAR models have strong external prediction performance. • The findings of CoMSIA were confirmed by molecular docking, then the binding modes were investigated. • For the purpose of identifying potential anti-breast cancer drugs, an in silico ADMET study was performed. • Molecular dynamics simulations were conducted on the most effective compound and the binding stability with the aromatase (3S7S) was validated using RMSD, RMSF, RoG, H-bond, and SASA calculations. • The docking results were confirmed by MM-PBSA evaluation. Breast cancer is a crucial global health issue, representing the most frequent cancer and a major cause of cancer-related mortality of women. The difficulty of treating this disease is compounded by increasing drug resistance, which complicates both the efficacy of current therapies and the costs associated with developing new therapeutic agents. Computer-aided drug design (CADD) therefore appears to be a promising solution for reducing the cost and time needed to develop breast cancer drugs. In this research, we investigated 47 thiosemicarbazone, 1,2,4-triazole and thioether derivatives as potential therapeutic agents for breast cancer. Using 2D and 3D quantitative structure-activity relationship (QSAR) methodologies, we established models that were rigorously validated by internal and external procedures to improve their predictive capabilities for new breast cancer treatments. The reliability of the selected descriptors was corroborated by molecular docking studies targeting aromatase, a key enzyme in the pathology of the disease. ADMET property evaluations further corroborated the pharmaceutical potential of the newly designed ligands. Molecular dynamics and MM-PBSA simulations carried out a detailed analysis of the ligands' binding stability with the studied enzyme. Among the newly designed compounds, the ligand C2 has shown to be a promising hit for breast cancer inhibition. Further experimental validation in the future will be necessary to fully explore its therapeutic potential in vitro and in vivo. [Display omitted] [ABSTRACT FROM AUTHOR]

• Acetyl quinolone thiosemicarbazone and its derivatives were synthesized by simple work up and column free products. • Phenyl ring substituted thiosemicarbazide 5b and 6b shows the good in-vitro antioxidant activity. • From the In-vivo embryo toxicity analysis, all the synthesized compounds had a less toxic. • The compound 5b and 6b shows the good binding energy for the protein 2C0U, 3NM8. In this study, we successfully synthesized a series of acetyl quinolone thiosemicarbazones (5a-d, 6a-d) using a simple work-up procedure yielding column-free products. The structures of the synthesized compounds were confirmed by various spectroscopic techniques, including 1H, 13C, and 2D NMR, along with FT-IR. Detailed 2D NMR analyses such as COSY, HSQC, and HMBC were also performed. The biological activities were evaluated through in-vitro, in-vivo , and in-silico studies. In-vitro antioxidant properties were assessed using radical scavenging assays, revealing significant activity for compounds 5b and 6b , likely due to the aromatic ring substitution in the thiosemicarbazide side chain. In-vivo zebrafish embryo toxicity studies indicated minimal toxicity for these compounds. Additionally, in-silico studies showed that compounds 5b and 6b have good binding energies for proteins 2C0U, 3NM8 and 2X08. Further the DFT study of HOMO and LUMO energy gap is small for 5b and 6b. These findings suggest that acetyl quinolone thiosemicarbazones are promising candidates for various biological applications due to their potent antioxidant activity and low toxicity. [Display omitted] [ABSTRACT FROM AUTHOR]

• A simple innovative two-step design for the synthesis of various biologically active xylenyl-spaced bis-dihydrazothiazoles derivatives using commercially available cabonyl compounds. • The coordination capacity of the new xylenyl-spaced bis-dihydrazothiazoles derivatives to chelate with Fe(III), Co(II), and Zn(II) transition metal ions was unambigiuosly confirmed via neutral tridentate complexation with a metal/ligand ratio of 2:1. • The antimicrobial screening of these new xylenyl-spaced bis-thiazole derivatives along with some of their metal complexes [M 2 L]; M=Fe, Co, or Zn, was conducted versus a group of six different microbial species using Gentamycin and Ketoconazole as antimicrobial standards. • Many of the new bis-thiazole derivatives along with some of their metal complexes showed outstanding inhibition versus the examined microbial species, most notably against C. albicans and E. coli , and A. fumigatus. • Amongst the three synthesized metal chelates [M 2 L], the zinc complex, [Zn 2 L] showed remarkable inhibition of both C. albicans and S. typhimurium and was notably more potent than the free ligand itself. Several new xylenyl-spaced bis-dihydrazothiazoles 6a-e and bis-dihydrazothiazolones 9a-e were synthesized by the simple reaction between bis-thiosemicarbazone 3 as a common synthetic scaffold, with two series of hydrazonoyl halides derivatives 4a-e and 7a-d. The chelation ability of these novel bis-dihydrazothiazole derivatives to perform as neutral tridentate ligands and coordinate to transition metal ions; Fe(III), Co(II), or Zn(II) through azomethine- N , thiazole- S , and azo- N atoms to form metal complexes with a metal/ligand ratio of 2:1 was elucidated. Diffused reflectance, magnetic moment, 1HNMR, FT-IR, TGA, and molar conductivity, were used to interpret the structures of all new xylenyl-spaced bis-heterocyclic compounds and their metal chelates. In-vitro , antibacterial and antiviral screening of these innovative xylenyl-spaced bis-dihydrazothiazole derivatives, as well as a selected group of their transition metal chelate complexes [M 2 L], were inspected, and the data was evaluated in comparison to those of Ketoconazole and Gentamycin as antimicrobial control standards using the agar well diffusion assay protocol against a selected group of fungal and bacterial species. Several compounds displayed respectable to great antimicrobial behavior against the examined microbial species. Bis-dihydrazothiazole 6c , particularly, showed exceptional inhibition of both C. albicans and E. coli. However, bis-dihydrazothiazolone 9b showed excellent inhibition of A. fumigatus. Additionally, amongst the three synthesized metal complexes [M 2 L] , only the zinc complex, [Zn 2 L] showed remarkable inhibition of both C. albicans and S. typhimurium and was even more potent than the free ligand, 9a itself. [ABSTRACT FROM AUTHOR]

• A series of novel Bi(III) complexes were synthesized and characterized. • Complex C4 effectively inhibited tumor growth and produced few side effects in vivo. • Complex C4 inhibits tumor growth by inducing apoptosis and inhibiting angiogenesis. While the currently available platinum-based antitumor drugs have severe side effects, there is a need to develop highly efficient and low-toxicity metal agents. In this study, we synthesized four bismuth (Bi) complexes (C1–C4) derived from 2-thiazolecarboxaldehyde thiosemicarbazones. These Bi(III) complexes showed significant antitumor activity, with C4 exhibiting the highest efficacy in structure–activity relationship studies. Notably, C4 effectively inhibited tumor growth and produced fewer side effects in vivo. We further confirmed the antitumor mechanisms of the C4 complex, which include inducing apoptosis, arresting the cell cycle at the S phase, inducing mitochondrial and its DNA damage, and suppressing angiogenesis. [ABSTRACT FROM AUTHOR]

• A novel series of 2-chloro pyridine-based thiosemicarbazones (3a-m) was synthesized. • Characterization of (3a-m) was done by 1H NMR, 13C NMR and mass spectrometric analysis. • Probed for inhibition potential as α-glucosidase inhibitors. • Compound 3m displayed highest inhibition activity with IC 50 value of 4.10 ± 0.16 µM. • Molecular docking studies were performed to find the binding mode of most potent inhibitor. Diabetes is a devastating metabolic illness that affects people of all ages and is widespread around the world as a result of the malfunctioning of prior treatment approaches. This work attempts to treat type 2 diabetes mellitus (T2DM) by outlining the design, synthesis, in vitro and in silico assessment of 2-Nicotinaldehyde-based thiosemicarbazones as possible inhibitors of α-glucosidase. The synthesized derivatives 3(a-m) displayed excellent to good inhibitory potential against standard drug acarbose (IC 50 = 4.10 ± 0.16 µM to 32.76 ± 0.80 µM. Among these compounds 3m displayed highest inhibition activity with IC 50 value of 4.10 ± 0.16 µM. SAR of the derivatives have shown that the compounds with meta substitution displayed better activity than the para substitution. In order to obtain more profound understanding, molecular dynamics, and in silico molecular docking simulations were performed to examine the interactions, stability, orientation, and conformation of the synthesized derivatives inside the α-glucosidase active pocket. [ABSTRACT FROM AUTHOR]

[Display omitted] A new polymer-analogous transformations of poly(N -vinylpyrrolidone) was used to prepare new complex-forming macromolecular systems containing thiourea and thio-semicarbazone sites. Two variants of modification were realized, namely, the method including the preliminary in situ activation of nucleophilic centres of the polymer amide fragments with dimethyl sulfate followed by introducing nucleophilic agents into the system, and the method including partial hydrolysis of poly(N -vinylpyrrolidone) followed by the amide coupling. The obtained modified polymeric materials react with silver ions in aqueous solution. [ABSTRACT FROM AUTHOR]

• CuS@CdS and CuS@ZnS nanocomposites have been successfully prepared by the hot injection method of thiosemicarbazone complexes as single source precursor. • The coupling of CuS with ZnS and CdS affected the surface morphology and optical properties of CuS@ZnS and CuS@CdS nanocomposites. • The coupling of CuS with ZnS and CdS improved the photocatalytic properties of CuS@ZnS and CuS@CdS nanocomposites under UV irradiation. • CuS@ZnS exhibits a significant enhancement photocatalytic compared to CuS@CdS. CdS and ZnS are considered excellent semiconductors for photocatalysis, but photocorrosion and low photocatalytic activity limit their practical application. In order to improve on their photocatalytic activities, Copper sulfide-decorated CdS and ZnS (CuS@CdS and CuS@ZnS) nanocomposites were synthesized from Cu(II), Zn(II) and Cd(II) complexes of 2–(phenyl(pyridin–2–yl)methylene)hydrazine–1–carbothioamide, as single source precursors using a facile hot injection method at 250 °C, employing olive oil as capping agent. The structure, morphology, and optical properties of the as-prepared nanocomposites were determined using various analytical techniques. The results of powder X-ray diffraction (p-XRD), energy dispersive X-ray spectroscopy (EDX) and elemental mapping showed the presence of CuS, CdS and ZnS in CuS@CdS and CuS@ZnS, confirming the formation of nanocomposites. Transmission Electron Microscopy (TEM) images show agglomeration of CuS nanoparticles on the surface of CdS and ZnS nanoparticles. Scanning electron microscopy (SEM) images of CuS@CdS and CuS@ZnS nanocomposites revealed an agglomerated flower-like structure with porous surface. The band gap energies of 2.84 eV and 3.12 eV for CuS@CdS and CuS@ZnS, respectively, obtained from Tauc plots, demonstrate that combining CuS with single CdS and ZnS has an effect on their optical properties which probably account for the improved photocatalytic responses. The photocatalytic performance of the as-prepared materials was evaluated using the photodegradation of methylene blue (MB) dye under UV light irradiation. Results show that the degradation efficiencies for CuS@CdS (57 %) and CuS@ZnS (65 %) nanocomposites exhibited higher photocatalytic activity compared to those of pure CuS (42.0 %), CdS (35.1 %) and ZnS (57 %), suggesting that thiosemicarbazone complexes can be used as precursors for the development of metal sulphide nanocomposites as useful photocatalysts for the degradation of organic pollutants. [ABSTRACT FROM AUTHOR]

A new pyrazole based thiosemicarbazone ligand, 5-methyl-3-formylpyrazole-N(4)-isopropylthiosemicarbazone, (HMP z NHPri) (compound I) , and its cobalt(III) and nickel(II) complexes, [Co(MP z NHPri) 2 ]Cl (compound II) and [Ni(HMP z NHPri) 2 ]Br 2 (compound III), respectively, have been synthesized and characterized through various physico-chemical and spectroscopic studies. Both the reported Co(III) and Ni(II) complexes are cationic in nature and behave as 1:1 and 1:2 electrolytes in MeOH, respectively. Electronic spectral features of the complexes have classified them as distorted octahedral ones. IR spectral data (4000–450 cm−1) have suggested a monoprotic tridentate (NNS) function of compound I coordinating to the Co(III) ion via the pyrazolyl (tertiary) ring nitrogen, azomethine nitrogen and thiolato sulphur atom; while for compound III , compound I has been found to act as neutral NNS tridentate one, coordinating to Ni(II) via the pyrazolyl iminic nitrogen, azomethine nitrogen and thioketo sulphur. Structural features of all the compounds are confirmed by the single crystal X-ray data. All the compounds reported here have been found to exhibit significant photocatalytic activity towards degradation of Methylene Blue (MB) under UV radiation. Anticancer activity of all the three compounds against cancer cell lines (HeLa and A549) and a normal cell line (HEK293) have been investigated. Compound II has been found to be more efficient against the human cervical cancer cell (HeLa) and the lung cancer cell (A549) than compounds I and III. The ligand and both the complexes display potential activities against both gram-positive (Bacillus subtilis MTCC 7193) and gram-negative bacteria (E. coli MTCC 1610). New Co(III) and Ni(II) complexes of a pyrazole containing Thiosemicarbazone ligand were synthesized and characterized. Their structures were determined by single crystal XRD study. Anticancer, antimicrobial and photocatalytic activities of all the compounds were investigated and discussed in detail. [Display omitted] • Syntheses and characterizations of new Co(III) and Ni(II) complexes have been reported • Single crystal XRD confirmed the structures of the ligand and its Co(III) and Ni(II) complexes. • All the compounds displayed significant photocatalytic activity in degrading MB. • The complexes exhibited efficient anticancer activity against HeLa and A549 cell lines. • The complexes showed potential antimicrobial activities against both gram+ve and gram-ve bacteria [ABSTRACT FROM AUTHOR]

Four Ru(II) complexes (A2 - A5) were synthesized from the reaction of coumarin Schiff base ligands (7da2-tsc , 7da3-mtsc , 7da4-etsc and 7da5-ptsc) with [RuHCl(CO)(PPh 3) 3 ]. The compounds were characterized by FT-IR, UV–Vis, 1H, 13C and 31P NMR, mass spectrometry and crystallographic analysis. Calf Thymus DNA (CT-DNA) binding studies revealed the intercalative mode of binding of the complexes with DNA. The results of Bovine serum albumin (BSA) binding studies established the interaction between BSA followed static quenching mechanism. The cytotoxic effects of the complexes and the ligands were evaluated against breast (MCF-7 and MDA-MB-231) and lung carcinoma cell lines (A549 and NCI-H460) using MTT assay. Complex A4 demonstrated potent cytotoxic effects on both breast and lung cancer cells. Furthermore, morphological observations and FACS analysis showed the decrease in cell density by complex A4 by induced morphological changes and apoptotic body formation and cell death in both breast and lung cancer cells. Moreover, the invertebrate model Caenorhabditis elegans was employed to assess the in vivo anticancer activity of compound A4. The findings indicated that the treatment with A4 reduced tumor development and significantly extended organismal lifespan by 64 % in the tumoral strain JK1466 without adversely affecting essential physiological functions of the worm. Additionally, A4 demonstrated an upregulation of two crucial antioxidant defense genes. Overall, these results suggested that the compound A4 can be a potential candidate with novel chemotherapeutic applications. The presented work focuses on four novel organoruthenium(II) complexes of 3-acetyl-7-diethylamino-2H-chromene-2-one- 4 N -substituted thiosemicarbazones. The biological activities like binding with Calf Thymus DNA (CT-DNA), Bovine serum albumin (BSA). The antiproliferation on breast (MCF-7 and MDA-MB-231) and lung carcinoma cell lines (A549 and NCI-H460) and in vivo anti-tumor activity were carried out. Synposis for graphical abstract Four Ru(II) complexes(A2 - A5) were synthesized by the reaction of coumarin Schiff base ligands (7da2-tsc , 7da3-mtsc , 7da4-etsc and 7da5-ptsc) with [RuHCl(CO)(PPh 3) 3 ]. The spectral techniques such as FT-IR, UV–Vis, 1H, 13C and 31P NMR, mass spectrometry and crystallographic analysis were used to characterize the compounds. Calf Thymus DNA (CT-DNA) binding studies of the complexes indicated an intercalative mode of binding with DNA. However, the binding studies with protein, Bovine serum albumin (BSA) revealed static quenching mechanism. The cytotoxic effects of these complexes, along with thiosemicarbazone ligands were evaluated against breast cancer cell lines (MCF-7 and MDA-MB-231) and lung carcinoma cell lines (A549 and NCI-H460) using the MTT assay. Complex A4 demonstrated potent cytotoxic effects on both breast and lung cancer cells. Furthermore, morphological observations and FACS analysis were performed. The results showed that the decreased cell density, induced morphological changes, apoptotic body formation, and cell death in both breast and lung cancer cells. Moreover, the invertebrate model Caenorhabditis elegans was employed to assess the in vivo anticancer activity of compound A4. The findings indicated that treatment with A4 reduced tumor development and significantly extended organismal lifespan by 64 % in the tumoral strain JK1466 without adversely affecting essential physiological functions. Additionally, A4 demonstrated an upregulation of two crucial antioxidant defense genes. Overall, these results suggest that the multifaceted compound A4 holds promise as a potential candidate for developing novel chemotherapeutic agents. Graphical abstract highlights organoruthenium(II) complexes; Coumarin Schiff base; Crystal structure; DNA/protein binding studies; MTT assay; FACS; Caenorhabditis elegans; Stress resistance. Graphical abstract caption Organoruthenium metallocycle induced mutation in gld-1 tumor suppression gene in JK1466 strain and appreciable lifespan expansion. [Display omitted] • Four organoruthenium(II) complexes have been synthesized and characterized. • Crystallographic study confirmed the structure of the ligands and complexes A3 & A5. • The morphological changes induced by the complexes on BSA were confirmed by scanning electron microscopy (SEM). • The cytotoxic potential of the complexes was evaluated against human breast cancer and human lung cancer cell lines. • In vivo studies on C.elegans validated the non-toxic nature of complex A4 on the growth and reproduction of the worms. [ABSTRACT FROM AUTHOR]

• Synthesis of hydrazone-based schiff base • Structural confirmation through various spectroscopic techniques • Exploration of electronic properties and optical nonlinearity via TDF • Study of electronic properties at M06/6–311G (d,p) functional A new thiosemicarbazide-based Schiff base (TSDHB) was synthesized from thiosemicarbazide and 2,3-dihydroxybenzaldehyde. The prepared thiosemicarbazone was characterized by elemental (CHN), FT-IR, 1H and 13C NMR techniques. Furthermore, the molecular structure was probed using the single-crystal X-ray diffraction (SC-XRD) technique, which confirmed the enol tautomeric form with two independent molecules in asymmetric unit. The dissimilarity between the molecular units was determined by molecular overlay plots. The various intermolecular interactions and solid-state assembly stabilization were explored by Hirshfeld surface analysis. Void analysis was executed to examine the mechanical stability of crystalline units. The bioactivity of thiosemicarbazone was probed with the help of its binding capacity with salmon sperm DNA (SS-DNA) by means of the absorption interaction method. Accompanied by biological activity, optoelectronic properties such as nonlinear optical properties of yielded crystal were also explored through the DFT approach at M06/6–311 G (d,p). For this, various kinds of investigations such as frontier molecular orbital (FMO), UV–Vis, global reactivity parameters (GRPs), transition density matrix (TDM), density of states (DOS), natural population analysis (NPA), and natural bond orbital analysis (NBO) were executed at M06 functional. A good agreement was examined between XRD and DFT findings of molecular geometric parameters. Notably, in comparison with urea, TSDHB demonstrated enhanced nonlinear optical properties (linear polarizability=4.766 × 10−23 esu and third-order hyperpolarizability=5.939 × 10−35 esu). These findings position TSDHB as a promising candidate for DNA binding as well as for photonic materials due to its unique molecular characteristics and enhanced nonlinear optical behavior. [ABSTRACT FROM AUTHOR]

• Synthesis, characterization of new diorganotin(IV) and triorganotin(IV) complexes. • The complexes were characterized by various physico-chemical and spectroscopic techniques. • DFT studies have also confirmed the geometry of complexes. • The synthesized compounds were investigated for their antibacterial activity. • Synthesized molecules have excellent non-linear optical properties. In this study, the antimicrobial and nonlinear optical (NLO) response of thiosemicarbazone, semicarbazone, and their organotin(IV) compounds have been investigated. Organotin(IV) complexes of various types, namely [R 2 Sn(PhTscz) 2 ], [R 2 Sn(Tscz) 2 ], [R 2 Sn(Scz) 2 ], [Bu 3 Sn(PTscz)], [Bu 3 Sn(PTscz)], and [Bu 3 Sn(Scz)] (where R = n-Butyl; methyl; PhTsczH = (±) 2-isopropyl-5-methyl-cyclohexylidene)-N-phenylhydrazine-carboxamide, TsczH = (±) 2-isopropyl-5-methylcyclo-hexylidene)hydrazinecarbothioamide, SczH = (±) 2-isopropyl-5-methylcyclohexyli-dene)hydrazine-carboxamide), were synthesized and characterized by CHN analysis, molar conductivity, UV-Vis, FTIR, and NMR (1H, 13C, 119Sn) spectroscopy, along with theoretical evidence obtained through density functional theory (DFT) simulations. The results showed that the Schiff base (HL) ligands acts as a bidentate NO/NS donor with azomethine nitrogen (N) and deprotonated ketonic oxygen/thionic sulphur (O, S) atoms. [R 2 Sn(L) 2 ] complexes are assigned a distorted octahedral structure, while Bu 3 Sn(L) complexes have distorted trigonal bipyramidal structures. The B3LYP/LanL2DZ programme theoretically discussed the electronic structure and nonlinear optical (NLO) properties of the synthesized compounds. The synthesised compounds were evaluated for antibacterial activity using the zone inhibition method. Antibacterial activity of the ligands and its metal complexes against Gram(+) and Gram(-) bacteria demonstrated that the organotin complexes are more potentially resistant to microbial activities than the free ligands. According to the reactivity parameter factors, compound Bu 2 Sn(Scz) 2 (3) is less reactive and more stable. Nonlinear optical (NLO) study revealed that compound (3) had greater linear polarizability (α) values, whereas compound Me 2 Sn(Scz) 2 (9) had higher first hyperpolarizability (β tot) values of 244.29 a.u. Because of their high initial hyperpolarizability values, these molecules have excellent non-linear optical properties and can be exploited as innovative materials in the construction of optoelectronic devices. [Display omitted] [ABSTRACT FROM AUTHOR]

Palladium and nickel complexes featuring thiosemicarbazones derived from chalcones and benzalketone were synthesized and fully characterized. Palladium compounds demonstrated remarkable antitumor efficacy against prostate (DU-145), breast (MCF-7), and non-tumor prostate (PNT2) cell lines. In contrast, the Ni(II) compound was inactive. Highlight the role of the metallic center for anticancer activity. Notably, these compounds did not interact significantly with DNA and Topoisomerase. [Display omitted] In this study, we report the synthesis and characterization of eight new palladium complexes and a nickel complex containing thiosemicarbazone ligands derived from chalcones and benzalketones. The techniques of Infrared and UV–visible spectroscopy, Nuclear Magnetic Resonance, Mass Spectrometry, and Elemental Analysis fully characterized the compounds. Crystallography was successful for five complexes and two ligands, allowing for X-ray Diffraction analysis. Molecular docking studies and assays involving DNA interaction via agarose gel electrophoresis and UV–Vis titration revealed no DNA interaction or inhibition of topoisomerase IIα enzyme activity. However, these compounds demonstrated potent cytotoxic effects (IC 50) against breast tumor (MCF-7) and prostate (DU-145) cell lines, as well as non-tumor prostate (PNT2) cell lines. These findings highlight the relevance of structural variations and the metallic center's nature in achieving cytotoxic effects, offering insights into the development of bioactive compounds. [ABSTRACT FROM AUTHOR]

• Novel thiosemicarbazones and semicarbazones were synthesized from chalcones. • Physicochemical methods (UV, IR, 1H, 13C NMR) were employed for identification. • Thiosemicarbazones have potent activity against gram-positive bacteria. • DFT was analyzed of key molecular descriptors. • Compounds 6 showed potent binding activity and ADMET properties. A series of new Schiff bases of semicarbazones and thiosemicarbazones have been derived from the condensation of symmetrical chalcones with semicarbazide and thiosemicarbazide, respectively. Various physicochemical and spectroscopic approaches (UV, IR, 1H, and 13C NMR) were used to fully describe the newly synthesized compounds. Schiff base derivatives were screened against bacterial strains viz. Bacillus Subtilis and Escherichia Coli. The DFT approach was also used to analyze some sensitivity descriptors alike chemical potential (µ), electronegativity (χ), hardness (η), and electrophilicity index (ω). Molecular docking was used to determine binding affinity of compounds with the desired protein. Compounds were identified to be more effective against Bacillus Subtilis than E. Coli. The molecular docking calculations of compound (6) exhibited the escalated binding affinity of -8.01 kcal/mol and binds with the active amino acids (Glu57 and Asp162). The prediction of in silico ADME properties discovered that synthesized molecules acquire significant drug-likeness properties. A series of new Schiff bases of semicarbazones and thiosemicarbazones have been derived from the symmetrical chalcones. Various physicochemical and spectroscopic methods (UV, IR, 1H, and 13C NMR) were used to fully describe the newly synthesized compounds. Schiff base derivatives were screened against bacterial strains viz. B. Subtilis and E. Coli. The DFT approach was also used to analyze some descriptors alike chemical potential(µ), electronegativity(χ), hardness(η), and electrophilicity index(ω). Molecular docking was used to determine binding affinity of compounds with the desired protein. Compounds were identified to be more effective against B. Subtilis than E. Coli. The molecular docking calculations of compound (6) exhibited the escalated binding affinity of -8.01 kcal/mol and binds with the active amino acids (GLU 57, ASP 162, ARG 88, PHE 35, VAL 59, ARG 160, ASP 84). The prediction of in silico ADME properties discovered that synthesized molecules acquire significant drug-likeness properties. [Display omitted] [ABSTRACT FROM AUTHOR]

• A series of benzaldehyde thiosemicarbazone analogues were synthesized. • 3,4-dihydroxy-5-nitrobenzaldehyde phenylthiosemicarbazide can effectively inhibit the activity of xanthine oxidase, with an IC 50 value of 0.0437uM. • 3,4-dihydroxy-5-nitrobenzaldehyde phenylthiosemicarbazide significantly reduces serum uric acid levels in high uric acid mice. • 3,4-dihydroxy-5-nitrobenzaldehyde phenylthiosemicarbazide did not exhibit significant biological toxicity. Uric acid, the metabolic product of purines, relies on xanthine oxidase (XOD) for production. XOD is a target for the development of drugs for hyperuricemia (HUA) and gout. Currently, treatment options remain limited for gout patients. 3, 4-Dihydroxy-5-nitrobenzaldehyde (DHNB) is a derivative of the natural product protocatechualdehyde with good biological activity. In this work, we identify a DHNB thiosemicarbazide class of compounds that targets XOD. 3,4-Dihydroxy-5-nitrobenzaldehyde phenylthiosemicarbazone can effectively inhibit XOD activity (IC50 value: 0.0437 μM) and exhibits a mixed inhibitory effect. In a mouse model of acute hyperuricemia, a moderate dose (10 mg/kg.w) of 3,4-dihydroxy-5-nitrobenzaldehyde phenylthiosemicarbazide effectively controlled the serum uric acid content and significantly inhibited serum XOD activity. In addition, 3,4-Dihydroxy-5-nitrobenzaldehyde phenylthiosemicarbazide showed favorable safety profiles, and mice treated with the target compound did not show any symptoms of general toxicity following a single dose of 500 mg/kg. In the allopurinol group, 50 % of the mice died. These results provide a structural framework and mechanism of XOD inhibition that may facilitate the design of hyperuricemia and gout treatments. [Display omitted] [ABSTRACT FROM AUTHOR]

The work reports the pharmacological applications of non-radioactive metal complexes with bis(thiosemicarbazones) and bis(hydrazone)-derived ligands. The antimicrobial, antiparasitic, and antineoplastic effects of these complexes, together with investigations into the interactions of some complexes with biological targets aiming at understanding their modes of action are described. The potential applications of copper(II) complexes with bis(thiosemicarbazones) for treating neurodegenerative diseases and studies on their mechanisms of action are also discussed. [Display omitted] The present work describes the multiple pharmacological applications of non-radioactive metal complexes with bis(thiosemicarbazones) and bis(hydrazone)-derived Schiff base ligands. The antimicrobial, antiparasitic, and antineoplastic effects of these complexes, together with investigations into the interactions of some complexes with biological targets aiming at understanding their modes of action are described. The potential applications of copper(II) complexes with bis(thiosemicarbazones) for treating neurodegenerative diseases and studies on their mechanisms of action are also discussed. [ABSTRACT FROM AUTHOR]

• [(E)-2-(2,6-dichlorobenzylidene)-N-ethylhydrazinecarbothioamide] from solvent free reaction. • Crystallization of the E -isomer as plates generated its stability in a solid state. • E -isomer inhibit the A549 and PC3 human cancer cells growth. • E -isomer is cytotoxic to PC3 (IC 50 = 2,51 ± 0,575 µM) and A549 (IC 50 = 4.75 ± 1.68 µM) cells. The E -isomer derived from thiosemicarbazone was obtained by reacting 4-ethylthiosemicarbazide with 2,6-dichlorobenzaldehyde. This compound was characterized by UV, IR and NMR spectrometry and its crystal structure was determined by single-crystal XRD. The cytotoxic activity of the compound was determined against PC3 (prostate cancer), A549 (human lung carcinoma) and U87MG (human glioblastoma) cells. The compound [ (E)-2-(2,6-dichlorobenzylidene)-N-ethylhydrazinecarbothiamide] inhibited the growth of PC3 (IC 50 = 2.51 ± 0.575 µM) and A549 (IC 50 = 4.75 ± 1.68 µM) cells. Compared with Ceramide (IC 50 = 10 µM) the thiosemicarbazone-induced inhibition of both cancer cell lines was found to be significant. [ABSTRACT FROM AUTHOR]

Antifouling compounds are used as paint components to mitigate biofouling on ships and submerged structures. One of the most known and used antifouling compounds is tributyltin (TBT). However, TBT is toxic to aquatic living beings, causing problems such as reduction of growth and imposex. The development of a TBT chemosensor could be of utter relevance in the building of an in-situ TBT monitoring device. Therefore, this work reports the synthesis of five new quinoline-based hydrazones (HZ) and two new quinoline-based thiosemicarbazones (TSC), with synthesis yields from 17 to 83 %. The compounds were tested in the presence of TBT, and some compounds of the group showed colorimetric or fluorimetric changes. The interaction between these compounds and TBT was tested by spectrophotometric or spectrofluorimetric titrations, which allowed to calculate the limit of detection (LOD) for each interaction. The fluorimetric interaction between HZ 4a and TBT was shown to be the most sensitive chemosensory method, with a LOD value of 1.7 μM. A Ridge classifier model was developed to correlate the ability for TBT detection and the modification of the structure of each molecule. The validity of the proposed model was tested by assessing the TBT-sensing ability of the two novel TSC 5a and 5b , which were synthesized after the development of the model. These two compounds also showed colorimetric changes in the presence of TBT, with LODs of 13.8 and 3.1 μM, respectively, in good accordance with the model's predictions. Further analysis of the model's decision process provided some insights on the desirable properties of the novel quinoline-derived TBT optical chemosensors. [Display omitted] • TBT is a toxic compound used on antifouling paints. • New quinoline-based hydrazones are reported as TBT chemosensors. • A machine learning-based model was developed for the design of TBT chemosensors. • Two quinoline-based thiosemicarbazones were synthesized as model validation. • The new chemosensors show detection limits in the order of μM. [ABSTRACT FROM AUTHOR]

A new single crystal of 4-(diphenylamino)benzaldehyde-4-(methyl)thiosemicarbazone, featuring a D-π-D molecular template was synthesized and utilized as an additive in solid biopolymer electrolytes mixed with carboxymethyl cellulose (CMC) and propylene carbonate (PC). The additive was structurally characterized using single-crystal X-ray diffraction. This revealed a triclinic crystal structure belonging to the triclinic space group, P 1 −. The lattice parameters were determined as follows: a = 6.942(6) Å; b = 11.409(11) Å; c = 12.442(10) Å; α = 91.024(16)°; β = 104.264(12)°; γ = 107.496(12)°; V = 906.4(13)Å3 and Z = 2. Notably, the additive exhibited extensive π-electron delocalization, leading to the formation of infinite chains through C-H-π interactions and intermolecular hydrogen bonding, ultimately resulting in an inverse centrosymmetric dimer in the form of the R 2 2 (8) motif. Furthermore, a detailed Hirshfeld surface analysis of the additive revealed significant contributions from C···H/ H···C, H···S/S···H and H···N/ N···H interactions with 20.7%, 11.2% and 3.7% of the total Hirshfeld surface analysis, respectively. These interactions indicate the potential of the additive to facilitate efficient electron transfer processes. The conductivity (σ) of the CMC–PC–additive system determined at ambient temperature was 8.00 ×10−9 Scm−1. The dielectric properties showed that the system follows the non-Debye behavior, in which the conductivity is predominantly due to ion conduction via the hopping mechanism. • A new single crystal of 4-(diphenylamino)benzaldehyde-4-(methyl)thiosemicarbazone additive, featuring a D-π-D molecular template, reveals a triclinic crystal structure with specific lattice parameters. • The additive exhibited extensive π-electron delocalization, forming infinite chains through C-H-π interactions and intermolecular hydrogen bonding. These interactions indicate its potential to facilitate efficient electron transfer processes. • The conductivity (σ) of the CMC–PC–additive system at ambient temperature was measured, and the dielectric properties of the system were also studied. The system's behavior was found to be predominantly due to ionic conduction via a hopping mechanism, following non-Debye behavior. [ABSTRACT FROM AUTHOR]

Two Ru(II)-benzene complexes encompassing two different coordination modes (monodentate S and bidentate N,S) of thiosemicarbazone were synthesized by tweaking the reaction conditions while using the same precursors. These complexes show multi-biological prospects. [Display omitted] • Synthesis and characterization of Ru(II)-benzene complexes with thiosemicarbazone. • Different coordinate modes of the same ligand with Ru(II)-benzene precursor on varying conditions. • Complexes showed good binding interactions with biomolecules. • The complexes exhibited potential anticancer activity in MDA-MB-231 cells. • Complexes induced activity via ROS-mediated mitochondrial apoptosis in cancer cells. Ru(II)-benzene complexes (P1 and P2) were synthesized using a thiosemicarbazone ligand (L1) in two different coordination modes, monodentate S and bidentate N,S, through carefully adjusted reaction conditions. Comprehensive characterization of the complexes was achieved through single crystal X-ray diffraction, revealing a piano-stool geometry around the Ru(II) ion. To evaluate the binding capabilities of the complexes towards CT DNA and BSA, UV–Vis and/or hydrodynamic methods were utilized. Docking studies further validated the intercalative binding mode with DNA, in agreement with the experimental findings, and identified specific BSA amino acids involved in the binding interactions. Based on the results of binding studies, cytotoxicity of the ligand and complexes was appraised in various cancer and normal cell lines alongside the commercial pharmaceutics. Complexes P1 and P2 displayed a promising activity against MDA-MB-231 [IC 50 = 5.11 (P 1) and 3.48 μM (P2)] and PANC-1 [IC 50 = 7.20 (P1) and 4.85 μM (P2)] cancer cells; with the bidentate system (P2) exhibiting a higher activity than its monodentate congener P1 , although both of them showed superior activity than the reference drugs. Various bioassays including Western blot analysis revealed the mode of cell death to be apoptosis, which was further concluded to be via the ROS-mediated mitochondrial signaling pathway. [ABSTRACT FROM AUTHOR]

[Display omitted] • Synthesis of N (4) heterocyclic substituted thiosemicarbazones and thiadiazoles. • DNA/BSA binding assays using absorption and emission spectroscopy. • Through molecular docking and dynamics studies, the ligands' ability to bind BSA were tested. • Drug-likeness (Swiss-ADME) and electronic structural characteristics (DFT) of TSL1–TSL4 were predicted. • Evaluation of cytotoxicity of TSL1-TSL4 against the A459, MCF7, HepG-2 cancer cells and normal Vero cells. Cancer's global impact necessitates innovative and less toxic treatments. Thiosemicarbazones (TSCs), adaptable metal chelators, offer such potential. In this study, we have synthesized N (4)-substituted heterocyclic TSCs from syringaldehyde (TSL1 , TSL2), and also report the unexpected copper-mediated cyclization of the TSCs to form thiadiazoles (TSL3 , TSL4), expanding research avenues. This work includes extensive characterization and studies such as DNA/protein binding, molecular docking, and theoretical analyses to demonstrate the potential of the as-prepared TSCs and thiadiazoles against different cancer cells. The DFT results depict that the thiadiazoles exhibit greater structural stability and reduced reactivity compared to the corresponding TSCs. The docking results suggest superior EGFR inhibition for TSL3 with a binding constant value of − 6.99 Kcal/mol. According to molecular dynamics studies, the TSL3 -EGFR complex exhibits a lower average RMSD (1.39 nm) as compared to the TSL1 -EGFR complex (3.29 nm) suggesting that both the thiadiazole and thiosemicarbazone examined here can be good inhibitors of EGFR protein, also that TSL3 can inhibit EGFR better than TSL1. ADME analysis indicates drug-likeness and oral availability of the thiadiazole-based drugs. The DNA binding experiment through absorption and emission spectroscopy discovered that TSL3 is more active towards DNA which is quantitatively calculated with a K b value of 4.74 × 106 M−1, K q value of 4.04 × 104 M−1and K app value of 5 × 106 M−1. Furthermore, the BSA binding studies carried out with fluorescence spectroscopy showed that TSL3 shows better binding capacity (1.64 × 105 M−1) with BSA protein. All the compounds show significant cytotoxicity against A459-lung, MCF-7-breast, and HepG2-liver cancer cell lines; TSL3 exhibits the best cytotoxicity, albeit less effective than cisplatin. Thiadiazoles demonstrate greater cytotoxicity than the TSCs. Overall, the promise of TSCs and thiadiazoles in cancer research is highlighted by this study. Furthermore, it unveils unexpected copper-mediated cyclization of the TSCs to thiadiazoles. [ABSTRACT FROM AUTHOR]

An extensive range of new biologically active morpholine based thiosemicarbazones derivatives 3a-r were synthesized, characterized by spectral techniques and evaluated as inhibitors of ENPP isozymes. Most of the novel thiosemicarbazones exhibit potent inhibition towards NPP1 and NPP3 isozymes. Compound 3 h was potent inhibitor of NPP1 with IC 50 value of 0.55 ± 0.02. However, the most powerful inhibitor of NPP3 was 3e with an IC 50 value of 0.24 ± 0.02. Furthermore, Lineweaver-Burk plot for compound 3 h against NPP1 and for compound 3e against NPP3 was devised through enzymes kinetics studies. Molecular docking and in silico studies was also done for analysis of interaction pattern of all newly synthesized compounds. The results were further validated by molecular dynamic (MD) simulation where the stability of conformational transformation of the best protein-ligand complex (3e) were justified on the basis of RMSD and RMSF analysis. [ABSTRACT FROM AUTHOR]

• 2-(1-(2-((4-fluorophenyl)amino)−4-methylthiazol-5-yl)ethylidene)hydrazine-1-carbothioamide derivatives (3–6) was designed and synthesized. • The antidiabetic activities of the new thiazole-thiosemicarbazone hybrids were screened in vivo for blood glucose lowering activity. • Compounds 5 and 6 were found the most potent to inhibit α -amylase and α -glucosidase. • PPAR- γ agonist activity for compound 5 and compound 6 was assessed. • In silico ADMET and docking studies were performed. In addition to Peroxisome Proliferator-Activated Receptor-gamma (PPAR- γ), which is essential for controlling type-2 diabetes mellitus, α -amylase and α -glucosidase inhibition is a key strategy in managing postprandial hyperglycemia. In this work a series of 2-(1-(2-((4-fluorophenyl)amino)-4-methylthiazol-5-yl)ethylidene)hydrazine-1-carbothioamide derivatives (3–6) was designed and synthesized through theiosemicarbazide derivatives, the structural elucidation of the new synthesized compounds was established using elemental and spectroscopic analyses. The antidiabetic activities of the new thiazole-thiosemicarbazone hybrids were screened in vivo for blood glucose lowering activity in normal rats and compared with pioglitazone as antidiabetic standard. Male Sprague-Dawley rats had reduced blood sugar levels after exposure to compounds 5 and 6 compared to pioglitazone. Additionally, the PPAR- γ agonist activity of compounds 5 and 6 as well as their ability to inhibit α -amylase and α -glucosidase were assessed. When compared to standard acarbose, which had an IC 50 value of 0.74 ± 0.15 mM/mL, compound 5 showed the highest α -glucosidase inhibitory activity with IC 50 value of 0.446 ± 0.01 mM/mL, while compound 6 showed good activity with an IC 50 value of 1. 914 ± 0.04 mM/mL. However, compound 5 and compound 6 had weak α -amylase inhibitory activity, with IC 50 values of 11.78 ± 0.58 and 24.18 ± 1.2 µg/mL respectively. Furthermore , Peroxisome proliferator activated receptor γ [PPAR- γ ] agonist activity for compound 5 and compound 6 was assessed and gave promising result as [PPAR- γ ] agonist with IC 50 value of 0.938 ± 0.023 and 0.947 ± 0.024 ng/mL respectively superior to that of pioglitazone with IC 50 value of 1.912 ± 0.11 ng/mL. All the results supported compound 5 as promising candidates for construction of new antidiabetic agents. Also, in silico ADMET and docking studies for the most promising derivatives 5, 6 , Acarbose, and Pioglitazone were done. [Display omitted] [ABSTRACT FROM AUTHOR]

• New (fac- [ Re (CO) 3 Br(HL)] compounds with bioactive indole and isatin-based thiosemicarbazones were synthesized. • The compounds showed potent antibacterial activity against the gram-positive Methicillin-resistant (MRSA) and Vancomycin-resistant (VRSA) S. aureus bacteria. • The (fac- [ Re (CO) 3 Br(HL)] species convert into dimer [Re 2 (CO) 6 (L) 2 ] in solution. • Re -thiosemicarbazonate complexes are dimers by re -s- re bridges as confirmed by single crystal x-ray diffraction. Antibiotic resistance is becoming a cause of serious concern to human health causing a significant impact on the global economy. The demand for novel antimicrobial agents is pressing since drug resistance is spreading and making antibiotics less and less effective. There is unrealized antibacterial potential in metal complexes. Among other compounds, rhenium complexes are particularly appealing because of their strong antibacterial activity and minimal in vivo toxicity. In this study, three Re carbonyl thiosemicarbazone (TSC) complexes were synthesized and characterized and their antibacterial potential was evaluated against various types of gram-positive and gram-negative bacteria. The structure of the ligands and their corresponding Re complexes were optimized at the DFT/B3LYP level of theory employing 6–311++ G (d,p) and LANL2DZ basis sets for C, H, N, O, S, and Re atoms respectively. The MS studies performed with time show that [ fac- [ Re (CO) 3 Br(HL)] was converted into dimer [Re 2 (CO) 6 (L) 2 ] in solution and the crystal structure of the dimer [Re 2 (CO) 6 (L) 2 ] obtained as the result of dimerization of the complex was solved. Among the three Re TSC complexes, [ fac- [ Re (CO) 3 Br(HL1)] exhibits the greatest antibacterial activity against S.aureus with MIC value 0.5 µg/mL. The data obtained showed that the synthesized complexes were ineffective against gram-negative bacteria but showed excellent antibacterial activity against gram-positive S.aureus. The [ fac- [ Re (CO) 3 Br(HL2)] complex derived from isatin-β-thiosemicarbazone showed lesser activity than the other two rhenium TSC complexes which were obtained by condensation of indole-2-carboxaldehyde and thiosemicarbazide. Furthermore, the in-silico molecular docking studies revealed that the binding energy of the docked compound [ Re (CO) 3 Br(HL)] with E. Coli and MRSA targets were extremely favorable (-7.18 and -5.67 kcal/mol, respectively which further demonstrates the potential of the synthesized complexes in the development of new antibacterial drugs. The molecular docking studies as well as experimental investigations demonstrate the effect of substituents on the ligand backbone on the antimicrobial activity of the synthesized rhenium carbonyl complexes. The enhanced antibacterial properties of rhenium carbonyl complexes with the TSC ligands in comparison to the ligand alone also suggest a possible synergistic effect of the metal center and the organic ligand. [Display omitted] [ABSTRACT FROM AUTHOR]

Three Ni(II) complexes of thiosemicarbazone, two mononuclear and one dinuclear, has been synthesized and X-ray crystallographically characterized. Each of the metal centers in 1 and 2 are found to have square planar geometries. 3 adopts octahedral geometry at its Ni(II) center. All the complexes show anti-cancer and anti-angiogenic activities. According to Chorio-Allantoic Membrane (CAM) assay, all the Ni(II) complexes are found to promote blood capillary growth by 18.18%, −10.7% and –22.7%, respectively in 24h. In aortic arch assay, complexes show the inhibitory effect of samples on the proliferation and migration of constituent cells namely endothelial cell, fibroblast and smooth muscle cell of the aortae. [Display omitted] Synthesis and X-ray structural characterization of three Ni(II) complexes of thiosemicarbazone ligand [Ni(L1) 2 ] (1), [Ni(L2)] 2 (2) and [Ni(L3) 2 ] (3) [L1 = 2-ethoxybenzaldehyde-N(4)-diethyl-3-thiosemicarbazone, L2 = o -vanillin-N(4)-diethyl-3-thiosemicarbazone and L3 = 2-benzoylpyridine-N(4)-diethyl-3-thiosemicarbazone] are reported. From the structural characterization data, the metal centers in 1 and 2 are found to have distorted square planar geometries but in 3 , the Ni(II) center adopts distorted octahedral geometry. The metal complexes (1 , 2 and 3) show anti-cancer and anti-angiogenic activities. The complexes act in dual mode by both inhibiting the growth of the cancer cells directly through inducing intracellular Reactive Oxygen Species (ROS) level and inhibiting the growth of blood vessels which can indirectly retard and inhibit tumor growth and progression. Angiogenesis assay performed in in vivo Chorio-Allantoic Membrane (CAM) assay indicated that the complexes significantly inhibited the blood capillary growth within 24 h. The anti-angiogenic effect was observed to be effective against all the key cells involved in angiogenesis namely endothelial cell, fibroblast and smooth muscle cell of the blood vessel as observed in aortic arch assay where the complexes exhibited inhibitory effect on aortic capillary sprouting. [ABSTRACT FROM AUTHOR]

[Display omitted] Five derivatives of thiosemicarbazide, classified as thiosemicarbazone type ligands (L1 - L5), were synthesized along with their respective bismuth(III) complexes (1–5), the latter using microwave irradiation. The ligands and complexes were characterized using various spectroscopic techniques, including IR, Raman, UV–Vis, 1H NMR, 13C NMR, EA, and ESI-mass. X-ray diffraction was also conducted to determine the crystal structures of ligands L1 , L2 , L4 , and L5 and bismuth complexes LBi1 and LBi4. All complexes displayed an octahedral geometry, with a single bismuth atom coordinating with the ligands via the sulfide atoms. Ligands L1-L5 and their complexes were evaluated against the Gram-negative species Salmonella spp. and the Gram-positive species Staphylococcus aureus using the Inhibition Zone (IZ) method to assess their antimicrobial potential. The results indicated that the synthesized bismuth(III) complexes exhibited promising inhibitory effects on the growth of Salmonella spp. [ABSTRACT FROM AUTHOR]

Thiosemicarbazone derivative molecules have proven to be good sensor materials in studies using various analytical methods. In this study, new ion–selective sensors were prepared using 2–furaldehyde thiosemicarbazone and their potentiometric properties were then tested. The newly developed copper(II)–selective sensors were successfully applied for the determination of copper(II) ion content in various environmental samples with very good performance. The data obtained with the developed sensor were compared with atomic absorption spectroscopy and it was determined that the results of both methods were compatible with each other. [Display omitted] Thiosemicarbazone derivative molecules have proven to be good sensor materials in studies using various analytical methods. In this study, new ion–selective sensors were prepared using 2–furaldehyde thiosemicarbazone and their potentiometric properties were then tested. The prepared sensors exhibited a very good selectivity towards copper(II) ions over various ions. Surface images and mappings of the prepared sensors were examined by scanning electron microscopy. Copper(II)–selective sensors had a Nernstian response of 28.5 ± 1.5 mV/decade, and a low detection limit of 6.89 × 10-6 mol L-1 over a wide concentration range of 1.0 × 10-5–1.0 × 10-1 mol L-1 (R 2 = 0.9992). The newly prepared copper(II)–selective sensors were shown to be produced reproducibly, stable and economically. The sensors, which can operate in a wide pH range of 5.0–9.0 without being affected by pH changes, had a fast response time of 5 s. The newly developed copper(II)–selective sensors were used as indicator electrodes for the potentiometric titration of copper(II) ions with ethylenediaminetetraacetic acid and were successfully applied for the determination of copper(II) ion content in various environmental samples with very good performance. The data obtained with the developed sensor were compared with atomic absorption spectroscopy and it was determined that the results of both methods were compatible with each other. [ABSTRACT FROM AUTHOR]

[Display omitted] The ability of substituted acenaphthenequinone-thiosemicarbazones to do complexation with Pd(II) and Ag(I) salts was investigated. The obtained Pd(II) 5a-f and Ag(I) 7a-f complexes showed that ligation was occurred during the reaction of two equivalents of the ligands with one equivalent of the metal salts. In case of Pd complexes 5a-f , two moles of HCl were eliminated during complexation process. Whereas direct ligation was occurred during complexation of one mole of AgNO 3 and two moles of ligands to form the corresponding cationic-anionic salts 7a-f. IR, NMR, and UV–vis spectra were used to deduce the structure of the formed metal complexes. X-ray structure analysis proved the syn -form of bis(bidentate) structure of Pd complex 5e , as Pd showed a square planar coordination with two sulfur and two nitrogen atoms. The cationic-anionic nature of silver complexes was revealed by molar conductance. UV–visible spectra were also investigated by means of Time-Dependent Density-Functional Theory (TD-DFT) computations. The obtained metal complexes were also investigated asantibacterial and antifungal agents. Compounds 5f , 5e , 7d , and 7f were found to be the most active and effective against the four bacterial strains, with compound 7f having the most potent action. Compound 7f (R = 3-OMe-Ph) showed MIC values of 0.066, 0.018, 0.018, and 0.033 µg/mL against B. subtilis, S. aureus , E. coli, and K. pneumoniae , respectively. For compound 7d (R = Benzyl), the MIC values are found as 0.028, 0.057, 0.028, and 0.028 µg/mL against the same previous bacterial strains. Compounds 5d , 5e , 7c , and 7f demonstrated promising antifungal activity against C. albicans with MIC values of 0.029, 0.023, 0.018, and 0.027 µg/ml, respectively, when compared to the reference fluconazole , which had a MIC value of 0.020 µg/ml. Compound 7f revealed inhibitory activity of E. coli DNA gyrase (IC 50 = 210 ± 15 nM, respectively) being 1.2-folds less potent than the reference novobiocin (IC 50 = 170 ± 20 nM). [ABSTRACT FROM AUTHOR]

• Synthesis and characterization: HACmMeTsc, HACmDEtTsc, [Cu(HACmMeTsc)Cl], [Cu(HACmEtTsc)Cl] and [Cu(HACmDEtTsc)Cl]. • [C u (HAC m M e T sc)C l ]: distorted square planar; hydroxy O, imine N, thione s atoms of HACmMeTsc and Cl− ion coordinated. • MTT assay: anticancer potency in dose dependent manner against two cancer cell lines: MCF-7 and MDA-MB-231. • Western blot analysis: down regulation of Bcl2 and upregulation of bax. • In silico : bioavailability; CYP1A2, CYP2C9 inhibitors/binding affinity (−6.8 to −8.4 kcal/mol) against EGFR and HER-2. Coumarin based thiosemicarbazones (TSC), (E)-2-(1-(4‑hydroxy-2-oxo-2 H -chromen-3-yl)ethylidene)- N -methylhydrazine-1-carbothioamide (HACmMeTsc) (3), (E)- N -ethyl-2-(1-(4‑hydroxy-2-oxo-2 H -chromen-3-yl)ethylidene)hydrazine-1-carbothioamide (HACmEtTsc) (4) and (E)- N,N ‑diethyl-2-(1-(4‑hydroxy-2-oxo-2H-chromen-3-yl)ethylidene)hydrazine-1-carbothioamide (HACmDEtTsc) (5) and their respective copper(II) complexes ([Cu(ACmMeTsc)Cl] (3a), [Cu(ACmEtTsc)Cl] (4a) and [Cu(ACmDEtTsc)Cl] (5a)) are synthesized and characterized by elemental analysis, FTIR, UV–Vis, ESI HRMS, 1H NMR, 13C NMR and single crystal X-ray diffraction analysis. The in vitro anticancer activity of the synthesized compounds by MTT assay against breast cancer cell lines MCF-7 and MDA-MB-231 exhibited strong anti-cancer potential in a dose dependent manner with IC 50 value in the range of 12.94 -23.70 μg/mL and 42.18- >100 μg/mL in MCF-7 and MDA-MB-231 cells respectively. Molecular docking study showed that compounds 3, 4 and 5 have significant binding affinity (ΔG = -6.8 to -8.4 kcal/mol) along with interactions including hydrogen bonding with active sites of amino acid residues of both studied proteins, EGFR and HER 2, which may be responsible for the inactiveness of the receptors. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • Coumarin Thiosemicarbazones: acidic hydrogen at N(1) involved in intramolecular hydrogen bonding with lactone carbonyl forming more stable E isomer than Z isomer. • Cu(II) complex: distorted square planar, carbonyl O, imine N, thiolate S−, and Cl− ion coordinated. • In Vitro : anticancer activity in dose dependent manner against MCF-7 and MDA-MB-231 cells. • In Silico : follows Lipinski's rule and high binding energy (−5.8 to −8.0 Kcal/mol) against EGFR and HER-2. A series of 3-acetylcoumarin-based thiosemicarbazones and their copper(II) complexes were synthesized and characterized by elemental analysis, IR, UV–Vis, HR-ESI Mass, NMR, EPR and single crystal XRD. The XRD study revealed thione tautomer for TSCs 3 (AcCmDEtTSC) and 4 (AcCmDPrTSC) whereas Cu(II) complex 8 [Cu(AcCmDPrTSC)Cl] has distorted square planar geometry around the metal ion. Compound 1 (AcCmMeHTSC) among the thiosemicarbazones (TSCs) was more effective against both breast cancer cell lines: MCF-7 (IC 50 ; 13.02 µg/mL) and MDA-MB-231 (IC 50; 42.71 µg/mL), whereas compounds 7 [Cu(AcCmDEtTSC)Cl] (IC 50; 32.84 µg/mL) and 8 [Cu(AcCmDPrTSC)Cl] (IC 50: 34.69 µg/mL) among the Cu(II) complexes were more effective against MDA-MB-231 cell lines. Anticancer activity of the test compounds enhanced in dose dose-dependent manner against both MCF-7 and MDA-MB-231 cells. Molecular docking study showed significant binding affinity of the test compounds, notably compound 2 (AcCmEtHTSC) with −7.1 kcal/mol and −8.0 kcal/mol, compound 3 with −7.3 kcal/mol and −7.8 kcal/mol against target proteins EGFR and HER2 respectively. Although the IC 50 value of the synthesized compounds is not very encouraging, their significant binding affinity values (−5.8 kcal/mol to −8.0 kcal/mol) against the target proteins EGFR and HER 2 is encouraging for the further exploration of their anticancer activity in the future. [ABSTRACT FROM AUTHOR]

• Fe 3 O 4 @SiO 2 -HAT-Cu(I) is a novel and efficient magnetic heterogeneous nanocatalyst. • Ease of preparation, stability, and cheapness of the catalyst. • Ease of the work-up procedure and catalyst separation by an external magnet field. • Reusability and potency of Fe 3 O 4 @SiO 2 -HAT-Cu(I) catalyst after several runs. • Use of green reaction media, simple performance, waste minimization, and atom-economy. A novel magnetically separable catalyst, the copper-hydroxyacetophenone thiosemicarbazone complex immobilized on silica-coated magnetite nanoparticles (Fe 3 O 4 @SiO 2 -HAT-Cu(I)), has been synthesized and characterized. The characterization included various techniques such as X-ray diffraction spectroscopy (XRD), energy dispersive X-ray spectroscopy (EDX), field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), dynamic laser scattering (DLS), thermogravimetric analysis (TGA), vibrating sample magnetometer (VSM), atomic absorption spectroscopy (AAS), inductively coupled plasma-optical emission spectrometry (ICP-OES), and Fourier-transform infrared spectroscopy (FT-IR). The catalytic activity of Fe 3 O 4 @SiO 2 -HAT-Cu(I) was evaluated in a green aqueous mediated three-component synthesis of 1,2,3‐triazles. The catalyst efficiently facilitated the 'Click' Huisgen cycloaddition reaction between alkynes, sodium azide, alkyl bromides and/or epoxides in water/THF at 70 °C, resulting in good to excellent yields of 1,4-disubstituted 1,2,3‐triazle derivatives. Fe 3 O 4 @SiO 2 -HAT-Cu(I) is a new, low-cost, and magnetically separable heterogeneous catalyst that can be easily prepared and reused for multiple reaction runs without significant loss of catalytic activity. Synthesis, characterization, and application of copper-hydroxyacetophenone thiosemicarbazone complex immobilized on silica-coated magnetite nanoparticles (Fe 3 O 4 @SiO 2 -HAT-Cu(I)) as a novel magnetically retrievable nanocatalyst for the three-component synthesis of 1,4-disubstituted 1,2,3-triazoles are described. [Display omitted] [ABSTRACT FROM AUTHOR]