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We have designed a series of 17 new 2-(trifluoromethyl)-1H-benzimidazoles based on alkylation with ethyl chloroacetate. The corresponding ester underwent saponification and hydrazinolysis to afford the corresponding acid and hydrazide, respectively. Hydrazide reacted with aromatic aldehydes and isothiocyanates and gave the corresponding hydrazones and thiosemicarbazide, respectively. The hydrazide and acid derivatives were used to attach an amine; primary and secondary amines via "DCC and azide coupling" methods to finally give a series of N-alkyl-2-(2-(trifluoromethyl)-1H-benzimidazol-1-yl)acetamides with a wide range of lipophilic and hydrophilic features. The most active compound was tested for cytotoxicity against MCF-7 cells using the MTT assay. Some compounds demonstrated activity against two proteins, interacting with key amino acids like the co-crystallized ligands such as compound 7d. Compound 7d exhibited potent cytotoxicity with an IC50 value of 0.51 μM compared to Doxorubicin (IC50 = 2.12 μM). [ABSTRACT FROM AUTHOR]

Over the years, several new medicinal substances have been introduced for the treatment of diseases caused by bacteria and parasites. Unfortunately, due to the production of numerous defense mechanisms by microorganisms and parasites, they still pose a serious threat to humanity around the world. Therefore, laboratories all over the world are still working on finding new, effective methods of pharmacotherapy. This research work aimed to synthesize new compounds derived from 3-trifluoromethylbenzoic acid hydrazide and to determine their biological activity. The first stage of the research was to obtain seven new compounds, including six linear compounds and one derivative of 1,2,4-triazole. The PASS software was used to estimate the potential probabilities of biological activity of the newly obtained derivatives. Next, studies were carried out to determine the nematocidal potential of the compounds with the use of nematodes of the genus Rhabditis sp. and antibacterial activity using the ACCT standard strains. To determine the lack of cytotoxicity, tests were performed on two cell lines. Additionally, an antioxidant activity test was performed due to the importance of scavenging free radicals in infections with pathogenic microorganisms. The conducted research proved the anthelmintic and antibacterial potential of the newly obtained compounds. The most effective were two compounds with a 3-chlorophenyl substituent, both linear and cyclic derivatives. They demonstrated higher efficacy than the drugs used in treatment. [ABSTRACT FROM AUTHOR]

[Display omitted] Thiazolidin-4-ones functionalized at the position 5 and their heterocycle-annulated analogues were obtained based on the reaction of thioureas with dialkyl acetylenedicarboxylates. In most cases the reaction proceeds with high selectivity to form 2-iminothiazolidin-4-one-type products. [ABSTRACT FROM AUTHOR]

Objectives. To develop the procedures for synthesis of hybrid molecules with potential anti-tubercular activity containing heterocyclic cores of 4-nitroimidazole and 1,3,4-thiadiazole within the framework of a double-drug strategy and predict bioactivity of target structures and drug-likeness physicochemical parameters.Methods. Target compounds were prepared by classical organic synthesis methods. The structure of the obtained compounds was characterized by melting points, 1H and 13C nuclear magnetic resonance spectroscopy, and high-resolution mass spectrometry. The calculation of the physicochemical parameters of the target compounds and prediction of their biological activity were carried out using publicly available software for cheminformatics and molecular modeling.Results. Acylation of propargylamine with (2-methyl-4-nitro-1H-imidazol-1-yl)acetic and (4-nitro-1H-imidazol-1-yl)acetic acids provided the corresponding amides, which were cyclized with seven different benzylamines in the presence of zinc triflate. In this way, seven new compounds were obtained at 20–30% yields. Ten arylamines were acylated with chloroacetyl chloride and the resulting chloroacetamides were converted into corresponding thio-oxahydrazides by the Willgerodt–Kindler reaction. Following acylation by (4-nitro-1H-imidazol-1-yl)acetic acid, these compounds were converted into the target hybrid imidazolyl-thiadiazoles at 29–54% yields.Conclusions. Two series of new heterocyclic compounds with a hybrid structure including a privileged 4-nitroimidazole moiety linked to the second heterocycle, imidazole, or thiadiazole, were obtained. The synthesis and characterization of compounds by physicochemical methods was aimed at searching for anti-tuberculosis activity. The bioactivity potential of target compounds was demonstrated by preliminary calculations performed using public prognostic programs.

A new method has been proposed for the synthesis of diphenylphosphinylformic acid hydrazide based on the reaction of phosphine oxide and trimethylchlorosilane in the presence of a tertiary amine, followed by the reaction with chloroformic acid ester and then hydrazine hydrate. The hydrazide fragment was modified into a thiosemicarbazide fragment by reacting diphenylphosphinylformic acid hydrazide with organic isothiocyanates. It was found that in an aqueous alkaline medium, thiosemicarbasides do not heterocyclize to 1,2,4-triazole-3-thiones, as expected. As a result of the P–C bond rupture, diphenylphosphinic acid and 5-thioxo-1,2,4-triazolidin-3-ones are formed. [ABSTRACT FROM AUTHOR]

This review focuses on some interesting and recent applications of transition metals towards the complexation of thiosemicarbazides, thiocarbohydrazides, and their corresponding carbazones. We started the review with a description of the chosen five metals, including Cu[Cu(I), Cu(II], Co(II), Ni(II), Pd(II), and Ag(I) and their electronic configurations. The stability of the assigned complexes was also discussed. We shed light on different routes describing the synthesis of these ligands. We also reported on different examples of the synthesis of Cu(I), Cu(II), Co(II), Ni(II), Ag(I), and Pd(II) of thiosemicarbazide and thiocarbohydrazide complexes (until 2022). This review also deals with a summary of the fruitful use of metal complexes of thiosemicarbazones and thiocarbazones ligands in the field of catalysis. Finally, this recent review focuses on the applications of these complexes related to their biological importance. [ABSTRACT FROM AUTHOR]

A new series of benzimidazoles including triazole and thiosemicarbazide moieties was synthesized and their urease inhibition studies were evaluated according to the method of Van Slyke and Archibald. Especially triazole derivatives have effective inhibition activities between 0.04±0.026 and 0.26±0.042 µM IC50 values. The best antiurease activities with IC50 0.04±0.026 and 0.06±0.033 µM belongs to 5-[(5,6-dichloro-1H-benzimidazol-1-yl)methyl]-4-nitrophenyl-4H-1,2,4-triazole-3-thiol and 2-[(2-benzyl-5,6-dichloro-1H-benzimidazol-1-yl)acetyl]-N-(4-nitrophenyl)hydrazinecarbothioamide, respectively. [ABSTRACT FROM AUTHOR]

Targeted therapies have come into prominence in the ongoing battle against non-small cell lung cancer (NSCLC) because of the shortcomings of traditional chemotherapy. In this context, indole-based small molecules, which were synthesized efficiently, were subjected to an in vitro colorimetric assay to evaluate their cyclooxygenase (COX) inhibitory profiles. Compounds 3b and 4a were found to be the most selective COX-1 inhibitors in this series with IC50 values of 8.90 µM and 10.00 µM, respectively. In vitro and in vivo assays were performed to evaluate their anti-NSCLC and anti-inflammatory action, respectively. 2-(1H-Indol-3-yl)-N′-(4-morpholinobenzylidene)acetohydrazide (3b) showed selective cytotoxic activity against A549 human lung adenocarcinoma cells through apoptosis induction and Akt inhibition. The in vivo experimental data revealed that compound 3b decreased the serum myeloperoxidase and nitric oxide levels, pointing out its anti-inflammatory action. Moreover, compound 3b diminished the serum aminotransferase (particularly aspartate aminotransferase) levels. Based on the in vitro and in vivo experimental data, compound 3b stands out as a lead anti-NSCLC agent endowed with in vivo anti-inflammatory action, acting as a dual COX-1 and Akt inhibitor. [ABSTRACT FROM AUTHOR]

Copyright of Proceedings of the YSU B: Chemical & Biological Sciences / Gitakan Teghekagir. K'imia, Kensabanut'yun is the property of Publishing House of Yerevan State University and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The paper contains the results obtained in grafting the acyl-thiosemicarbazide on the holder molecule 5-nitro-benzimidazol-2-sulfonyl-acetic acid by oxidation reaction of 5-nitro-benzimidazol-2-yl-mercapto-acetic acid, then passed to the corresponding sulfonyl hydrazide. Acyl-thiosemicarbazides containing the sulfonyl group were obtained. The chemical structure of the newly obtained compounds was confirmed by spectral analysis (FT-IR, 1H-NMR). This article aims with spectral and quantum-chemical characterization of three new thiosemicarbazides with potential tuberculostatic action. The reaction way, the main IR and NMR peaks and the quantum-mechanical parameters, computed with Spartan'14 program are estimated. The tuberculostatic of action is analyzed compared with reference drug isoniazid. [ABSTRACT FROM AUTHOR]

Enzyme inhibitors are vital aspects for studying enzymes and are employed as drugs to treat certain disorders, thus implying pivotal role in drug discovery. In the current study, a series of triazole compounds 4(a-o) were synthesised to explore their inhibitory potential against α-glucosidase and urease enzymes. These derivatives with dichlorophenyl substituents were prepared by cyclization of thiosemicarbazides and their structures were confirmed through spectroanalytical techniques. The in vitro biological screening revealed that the compounds 4a, 4b, 4k, 4l, 4m, 4o having IC50 values of 121.09 ± 1.25, 137.22 ± 0.22, 110.4 ± 2.4, 114.79 ± 1.1, 146.72 ± 1.29, 94.21 ± 0.15 [µM] respectively, exhibited good potential α-glucosidase inhibition, in comparison to Acarbose: IC50 51.23 µM, while the compounds 4a, 4b, 4c, 4k, 4l, having IC50 values of 48.52 ± 0.39, 52.22 ± 1.37, 60.98 ± 0.34, 37.06 ± 0.51, 38.66 ± 1.7 [µM] respectively exhibited good potential for urease inhibition near to standard(Thiourea: IC50 24.14 [µM]). These in vitro findings were accompanied further by molecular docking simulations, which revealed significant binding interactions of the synthesized derivatives within the active sites of the enzymes.

Based on the results of previous work, we designed and synthesized 1,3,4-thiadiazole derivatives. The cytotoxic activity of the obtained compounds was then determined in biological studies using MCF-7 and MDA-MB-231 breast cancer cells and a normal cell line (fibroblasts). The results showed that all compounds displayed weak anticancer activity towards two breast cancer lines: an estrogen-dependent cell line (MCF-7) and an estrogen-independent cell line (MDA-MB-231). The compound most active towards MCF-7 breast cancer cells was SCT-4, which decreased DNA biosynthesis to 70% ± 3 at 100 µM. The mechanism of the anticancer action of 1,3,4-thiadiazole was also investigated. We choose a set of the most investigated proteins, which are attractive anticancer targets. In silico studies demonstrated a possible multitarget mode of action for the synthesized compounds but the most likely mechanism of action for the new compounds is connected with the activity of caspase 8. [ABSTRACT FROM AUTHOR]

The effect of the structural features of the starting thiosemicarbazides as well as the cyclization reaction conditions on the chemo- and regioselectivity of the formation of heterocyclic systems is discussed. [ABSTRACT FROM AUTHOR]

A novel series of thiosemicarbazide-substituted coumarins was synthesized and the inhibitory effects against four physiologically relevant carbonic anhydrase isoforms I, II, IX and XII showed selective activities on the tumor-associated IX and XII isozymes. Molecular modeling studies on selected compounds 14a and 22a were performed. The binding modes of such compounds were determined assuming their enzymatically active structures (i.e., cinnamic acid) in the thermodynamically favored, and not previously explored, E geometry. Molecular modelling suggests multiple interactions within the enzymatic cavity and may explain the high potency and selectivity reported for the hCAs IX and XII. [ABSTRACT FROM AUTHOR]

A novel biologically active thiosemicarbazide derivative ligand L (N-[(phenylcarbamothioyl)amino]pyridine-3-carboxamide) and a series of its five metal(II) complexes, namely: [Co(L)Cl2], [Ni(L)Cl2(H2O)], [Cu(L)Cl2(H2O)], [Zn(L)Cl2] and [Cd(L)Cl2(H2O)] have been synthesized and thoroughly investigated. The physicochemical characterization of the newly obtained compounds has been performed using appropriate analytical techniques, such as 1H and l3C nuclear magnetic resonance (NMR), inductively coupled plasma (ICP), thermogravimetric analysis (TGA), Fourier-transform infrared spectroscopy (FTIR) and magnetic measurements. In order to study the pharmacokinetic profile of the compounds, ADMET analysis was performed. The in vitro studies revealed that the synthesized compounds exhibit potent biological activity against A549 human cancer cell line. [ABSTRACT FROM AUTHOR]

A series of 28 novel naproxen derivatives (4a-f, 5a-f, 6a-d, 7a-f, and 8a-f) have been designed, synthesized, and characterized. The synthesized derivatives were assessed as dual inhibitors for 15-lipoxygenase (LOX) and α-glucosidase enzymes and checked for cytotoxicity and ADME studies. The inhibitory potential of naproxen derivatives for 15- LOX was checked through two different methods, the UV absorbance method and the Chemiluminescence method. The biological activities result revealed that through the UV absorbance method, compound 4f (IC50 21.31 ± 0.32 µM) was found potent among the series followed by compounds 4e (IC50 36.53 ± 0.51 µM) and 4d (IC50 49.62 ± 0.12 µM) against standard drug baicalein (IC50 22.46 ± 1.32 µM) and quercetin (IC50 2.34 ± 0.35 µM), while through chemiluminescence method tested compounds showed significant 15-LOX inhibition at the range of IC50 1.13 ± 0.62 µM −123.47 ± 0.37 µM. Among these compounds, 4e (IC50 1.13 ± 0.62 µM), 5b (IC50 1.19 ± 0.43 µM), 8c (IC50 1.23 ± 0.35 µM) were found most potent inhibitors against quercetin (IC50 4.86 ± 0.14 µM), and baicalein (IC50 2.24 ± 0.13 µM). The chemiluminescence method was found more sensitive than the UV method to identify 15-LOX inhibitors. Interestingly all synthesized compounds showed significant α-glucosidase inhibitory activity (IC50 1.0 ± 1.13 µM − 367.2 ± 1.23 µM) even better than the standard drug acarbose (IC50 375.82 ± 1.76 µM), while compound 6c (IC50 1.0 ± 1.13 µM) and 7c (IC50 1.1 ± 1.17 µM) were found most potent compounds among the series even many folds better than the standard drug. The cell viability results showed that all compounds were less toxic, maintained cellular viability at the range of 99.8 ± 1.3% to 63.7 ± 1.5%. ADME and molecular docking studies supported drug-likeness and binding interactions of compounds with the targeted enzymes.

We report herein anti-proliferation effects of 4-arylthiosemicarbazides, with a cyclopentane substitution at N1 position, on highly virulent RH strain of Toxoplasma gondii. Among them, the highest in vitro anti-Toxoplasma activity was found with the meta-iodo derivative. Further experiments demonstrated inhibitory effects of thiosemicarbazides on tyrosinase (Tyr) activity, and good correlation was found between percentage of Tyr inhibition and IC50Tg. To confirm the concept that thiosemicarbazides are able to disrupt tyrosine metabolism in Toxoplasma tachyzoites, the most potent Tyr inhibitors were tested for their efficacy of T. gondii growth inhibition. All of them significantly reduced the number of tachyzoites in the parasitophorous vacuoles (PVs) compared to untreated cells, as well as inhibited tachyzoites growth by impeding cell division. Collectively, these results indicate that compounds with the thiosemicarbazide scaffold are able to disrupt tyrosine metabolism in Toxoplasma tachyzoites by deregulation of their crucial enzyme tyrosine hydroxylase (TyrH).

Regioselective synthesis of quinolone-1,2,4-triazoles was established starting from 4-hydroxyquinol-2-ones. The strategy started by the reaction of ethyl bromoacetate with 4-hydroxyquinoline to give the corresponding ethyl oxoquinolinyl acetates, which reacted with hydrazine hydrate to afford the hydrazide derivatives. Subsequently, hydrazides reacted with isothiocyanate derivatives to give the corresponding acyl thiosemicarbazides. Finally, subjecting the thiosemicarbazide derivatives with ethyl bromoacetate, the reaction underwent internal cyclization and alkylation processes. Alkylation occurred regioselectivity to the sulfur atom of the thione group and not to the amino group. Thus 3-S-1,2,4-triazole-quinolones were obtained in good yields. The structure of the obtained compounds was proved by different spectroscopic techniques together with elemental analysis and X-ray crystallography. Synthesis of novel quinoline-2-one/1,2,4-triazole hybrids in four steps. NMR, IR and mass spectra together with elemental analysis and X-ray crystallography proved the structure of 3-S-alkylated-1,2,4-triazole-quinolones and excluded the formation of 2-N-alkylated-1,3,4-thiadiazole-quinolones. Plausible mechanism for the formation of the targeted compounds was suggested. [ABSTRACT FROM AUTHOR]

Aluminum (Al), one of the most comercially used metals is also susceptible to corrosion like iron and zinc when subjected to corrosive environments, either in the industries or during applications in general. One major method of controlling corrosion of Al is through the use of inhibitors which are usually compounds containing heteroatoms, conjugated systems or which are relatively large in size. One of such inhibitors, thiosemicarbazide derivatives were reported in literature as an Al inhibitor in 2M HCl solution through experimental studies. In this study, computational methods were used to further provide an indepth explanation into the mode and mechanism of the thiosemicarbazides inhibition on Al surface. Parameters including quantum chemical through DFT and molecular dynamic simulations of studied molecules on Al surfaces were conducted. Results obtained through calculation of adsorption or binding energies of these thiosemicarbazides were in good agreement with the experimentally reported results elsewhere. With respect to the calculated adsorption or binding energies, thier relatively low values infered that the compounds are weakly adsorbed onto the surface of Al through Van der Waals forces and therefore obey the mechanism of physical adsorption. It was also established that the reference molecule thiosemicarbazide (TSC) was least adsorbed when compared to the other five molecules of its derivatives. The order of the inhibition efficiency as determined is as follows: PBT>DTC>DPT>PCT>PTC>TSC.

We report herein anti-proliferation effects of 4-arylthiosemicarbazides, with a cyclopentane substitution at N1 position, on highly virulent RH strain of Toxoplasma gondii. Among them, the highest in vitro anti-Toxoplasma activity was found with the meta-iodo derivative. Further experiments demonstrated inhibitory effects of thiosemicarbazides on tyrosinase (Tyr) activity, and good correlation was found between percentage of Tyr inhibition and IC50Tg. To confirm the concept that thiosemicarbazides are able to disrupt tyrosine metabolism in Toxoplasma tachyzoites, the most potent Tyr inhibitors were tested for their efficacy of T. gondii growth inhibition. All of them significantly reduced the number of tachyzoites in the parasitophorous vacuoles (PVs) compared to untreated cells, as well as inhibited tachyzoites growth by impeding cell division. Collectively, these results indicate that compounds with the thiosemicarbazide scaffold are able to disrupt tyrosine metabolism in Toxoplasma tachyzoites by deregulation of their crucial enzyme tyrosine hydroxylase (TyrH). [ABSTRACT FROM AUTHOR]

Practical synthesis and biological activities of quinazolinyl–triazinyl semicarbazides (10a–j) and quinazolinyl–triazinyl thiosemicarbazides (11a–j) have been described. The novel semicarbazides and thiosemicarbazides were prepared by condensation of different nucleophiles like isocyanate and isothiocyanate by the displacement of chlorine atoms on the basis of functionality concept on varying conditions. The synthesized quinazolinyl–triazinyl semicarbazide and thiosemicarbazide derivatives were evaluated for their expected antimicrobial activity. All the final synthesized derivatives were characterized by their melting point, mass spectra, 1H NMR and 13C NMR as well as elemental microanalysis. The final analogues were then analyzed for their in vitro antimicrobial activity against bacteria (Gram positive and negative) and fungus using the agar streak dilution method as well as in vitro anti-HIV activity against two types of viral strains, viz. HIV type I (IIIB) and type II (ROD) by using MTT assay method. SAR and HOMO–LUMO studies were also carried out for proving the structural biological activity. Among them, compounds 10e, 10f, 11h and 11j gave best results as their energy gap is very low which makes their activity higher. [ABSTRACT FROM AUTHOR]

According to a WHO report from 2020, cancer constitutes one of the leading causes of death worldwide. The number of cancer deaths is estimated to be approximately 10 million per year. These epidemiological data confirm that cancer is an increasingly global healthcare problem that needs urgent action. From a biological point of view, the basic feature of cancer is the uncontrolled growth and spread of abnormal cells from the place of origin to another part of the body. Inhibition of uncontrolled proliferation is one of the main goals of anticancer therapy. During our preliminary studies, we identified a group of thiosemicarbazide-based human DNA topoisomerase II inhibitors that decreased the viability of cancer cells and inhibited intracellular biosynthesis of their DNA much stronger than etoposide, i.e., clinically relevant topoisomerase II inhibitor. What is also important isthat the investigated compounds were recognized as topoisomerase II poisons because of their ability to stabilize the DNA-topoII cleavable complex. The investigated thiosemicarbazide derivatives were examined as potential anticancer agents against a panel of ten cancer cell lines. Moreover, we have discovered and described the first-in-class dual inhibitors of human DNA topoisomerase II/indoleamine-2,3-dioxygenase 1 (IDO1) that can lead to the future use of thiosemicarbazide derivatives as relevant components of anticancer immunotherapy.

Thiophene containing thiazolyl carbohydrazide on reaction with various aryl isothiocynates yields thiosemicarbazides which were transformed into 1,2,4-substituted thiazoles by Hantzsch synthesis and characterized by spectral methods. Most of the synthesized new thiosemicarbazides are found to be promisingly effective against tested bacterial strains and exhibited moderate activity tested fungal strains. Most of the 1, 2, 4-substituted thiazoles are weakly active against test organisms. [ABSTRACT FROM AUTHOR]

Thiosemicarbazones which previously characterized as a new class that inhibit anti-bovine viral diarrhea virus (BVDV) prompted us for synthesizing a series of new thiosemicarbazone derivatives. Thus, in this study, we reported the synthesis and antiviral evaluation of a series of 5-(arylazo)salicylaldehyde thiosemicarbazone derivatives for their expected antiviral activity. The desired products were synthesized from the condensation of 5-(arylazo)salicylaldehyde derivatives with N-(4)-substituted thiosemicarbazide derivatives. Antiviral screening was performed to test the anti-bovine viral diarrhea virus properties. From the obtained results, compounds 5, 23 and 24 showed highly selective activity against BVDV by blocking the viral RNA synthesis in cell culture. The BVDV in antiviral drug studies is valuable surrogate for the hepatitis C virus (HCV); so, the above results provided a novel candidate for the development of anti-HCV agents. [ABSTRACT FROM AUTHOR]

2-Mercapto-1,3,4-triazoles and 2-amino-1,3,4-thiadiazoles were synthesized by successive transformations of 5-arylisoxazole- and 4,5-dichloroisothiazole-3-carboxylic acids and their derivatives. The amino group of 5-(4,5-dichloroisothiazol-3-yl)-1,3,4-thiadiazol-2-amine was acylated with 5-phenylisoxazole-3-carboxylic acid chloride. Simple approaches to the preparation of previously unknown heterocyclic assemblies containing two or three azole rings with a high potential for biological activity are described. [ABSTRACT FROM AUTHOR]

Products of interaction between alkylhydrazines and ethyl-, allyl-, and phenylisothiocyanates are studied using mass spectrometry in the modes of electron impact ionization and matrix-assisted laser desorption/ionization in combination with gas and liquid chromatography. Conditions for the chromatographic separation of reaction mixtures and mass spectrometric identification of target compounds in real-time and delayed modes are optimized. The physicochemical characteristics of the sorption of thiosemicarbazides are determined. The decomposition and fragmentation of their metastable protonated molecules are studied. Schemes are proposed for the formation of fragmented and characteristic thiosemicarbazide ions in different modes of ionization. [ABSTRACT FROM AUTHOR]

Synthesis of heteropropellanes in one step: the reaction between dicyanomethylene-1,3-indanedione (CNIND) and N-substituted-2-(2,4-dinitrophenyl)hydrazinecarbothioamides, furnished (3aR,8bS,Z)-2-amino-9-substituted-10-(2-(2,4-dinitrophenyl)hydrazono)-4-oxo-4H-3a,8b-(epithiomethanoimino)indeno[1,2-b]furan-3-carbonitrile as a type of (2,4-dinitrophenyl)hydrazono[3.3.3]propellanes in good yields as single diastereomers. Structure determination and confirmation of the synthesized products have been achieved using various and modern spectroscopic techniques such as IR, NMR (1H NMR and 13C NMR), mass spectrometry, as well as X-ray crystal analysis. The X-ray structure data cleared that the molecule of 7a was crystalized as monoclinic, space group C2/c (no.15). [ABSTRACT FROM AUTHOR]

Unusual reaction proceeding via the electrophilic activation of nitroalkanes in the presence of polyphosphoric acid has been discovered. Subsequent nucleophilic attack with semicarbazides or thiosemicarbazides allows to access 2-amino-1,3,4-oxadiazoles and 2-amino-1,3,4-thiadiazoles, respectively. [ABSTRACT FROM AUTHOR]

Schiff-base–bearing new bis(thiosemicarbazone) derivatives were prepared from terephthalaldehyde and various thiosemicarbazides. FT–IR, ¹H NMR, 13C NMR, and UV–Vis spectroscopic methods and elemental analysis were used to elucidate the identification of the synthesized molecules. The in vitro antioxidant activity of the synthesized compounds was analysed with the 1,1-diphenyl-2-picryl hydrazyl free-radical–trapping process. The synthesized compounds exhibited lower antioxidant activity than the standard ascorbic acid. IC50 values of the synthesized molecules measured from 3.81 ± 0.01 to 29.05 ± 0.11 µM. Among the synthesized compounds, compound 3 had the best antioxidant activity. Moreover, this study explained the structure activity relationship of the synthesized molecules with different substituents in radical trapping reactions. [ABSTRACT FROM AUTHOR]

The synthesis of 4-substituted 2-(2-arylhydrazinyl)thiazol-3-ium bromides and 4-aryl-2-(substituted amino)-3-(phenylamino)thiazol-3-ium bromide derivatives in high yields from the interaction of mono- and di-substituted thiosemicarbazides with phenacyl bromide derivatives is reported. The synthesized products have been elucidated using various spectroscopic tools such as IR, NMR, and mass spectrometry. Also the structure of three of the obtained compounds have been confirmed using X-ray crystallographic analyses, which showed that compounds 2-[2-(2,4-dinitrophenyl)hydrazinyl]-4-phenylthiazol-3-ium bromide and 4-phenyl-2,3-bis(phenylamino)thiazol-3-ium bromide crystals have a monoclinic shape and belonged to space group P21/c, whereas the crystals of 4-phenyl-2-(2-tosylhydrazinyl)thiazol-3-ium bromide show an orthorhombic shape with the space group Pbca [ABSTRACT FROM AUTHOR]

Synthesis of alkyl ((5‐[alkylamino]‐1,3,4‐thiadiazol‐2‐yl)methyl)carbamodithioates via the reaction of glycine‐based dithiocarbamates with thiosemicarbazides in the presence of POCl3 in ethanol is disclosed. The main advantages of this method including the use of ethanol as solvent, no need to column chromatography for purification and high to excellent yields of products are noteworthy. [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]

[Display omitted] • Mono and binuclear stable metal chelates with bio-potent novel Schiff base ligands of N, O and S donors are engrossed. • Thiosemicarbazides and 1,3,4 thiadizole have been advanced for copious biological investigations. • Chelation, structure diversity and stability of metal complexes prompt in reinforcement the antimicrobial potency of metal complexes. • Assessment executed for biological potential of synthesized Schiff base ligands and complexes. Metal complexes of Schiff base ligands (exhibit imine -C = N- functional group) derived from thiosemicarbazide and 1,3,4 thiadiazole have attracted the attention of researchers on account of excellent broad range applications in a variety of fields from material sciences to biological sciences. Broad range of factors such that involvement of N, S, and O donor atoms, chelating property, chemical adaptability, minimum toxicity owing to -N-C = S linkage, structure topologies and diversity, polydentate ligands, aromaticity, extended conjugations in 1,3,4 thiadiazole and stability accommodate pharmacological potential. Widespread organic precursors (aromatic aldehyde and primary amine) have been used for the development of novel Schiff base ligands and metal complexes. Metal chelates inclusive of d-block transition metals and non-transition metals with broad distinct features have also been synthesized and evaluated via various classical and advanced spectral and analytical techniques. This review encompasses the synthesis, spectral studies and investigations that have been reported for Thiosemicarbazides, 1,3,4 thiadiazole Schiff base derivatives of transition metal complexes followed by evaluation of wide variety of biological applications. This review summarizes advancements in research over the last 15 years (2007–2022). [ABSTRACT FROM AUTHOR]

In present work, one-pot synthesis of some new 2,4-disubstitued thiazolyl pyrazole derivatives was carried out. The reaction of different pyrazole 4-carbalaldehydes, thiosemicarbazides and α-haloketones in one pot afforded the target molecules. The synthesis was carried out via two methods: one conventional method, whereby pyrazole 4-carbaldehydes, thiosemicarbazides, and α-haloketones were refluxed in ethanol; and a second way, where the reaction mixture was ground at RT. The rate of the reaction, yield of the products, and purity of the products were compared for both methods. All of the synthesized compounds were tested for their antimicrobial activities. It was found that most of the compounds showed good-to-moderate antibacterial as well as antifungal activities.

PdL1,2Cl2·H2O (I, II) and CuL1Cl2·H2O (III) complexes (L1 and L2 are 1-terpenyl-3-thiosemicarbazides of pinane and para-menthane series, respectively) are obtained. Single crystals of complexes I and [PdL3Cl2] (IV) (L3 is the product of hydrochlorination of ligand L2) have been grown. According to XRD data, crystal structures of I, IV consist of complex cations [PdLCl]+ and outer-sphere anions Cl−. The coordination polyhedron N2SCl is a distorted square. L1 and L3 are tridentate ligands. Free ligands L1, L2 and complexes I-III are studied using IR spectroscopy; conclusions on the structure of the Cu(II) complex are inferred from the analysis of obtained data. Cytotoxic properties of L1, complexes I and III, as well as the carboplatin pharmaceutic are studied on the Hep2 (human larynx carcinoma) cell line. Complexes I and III are shown to be moderately cytotoxic: they are twice as less toxic with respect to Hep2 cells than carboplatin that is used in the experiment as the reference complex. [ABSTRACT FROM AUTHOR]

Thiosemicarbazide derivatives (TSC, N-Phenyl TSC, N-Cyclohexyl TSC) doped polypyrrole (PPy) based electrodes were synthesized in one step electropolymerization method. It was determined that thiosemicarbazide derivatives had an effect on the morphological and chemical structure of PPy. Among the thiosemicarbazide derivatives, it was determined that the additive of PPy that had the highest and most curative effect on the electrochemical energy storage performance was determined to be N-Cyclohexyl TSC, and its effects on the electrochemical performance at different concentrations were investigated. The PPy/N-Cyclohexyl TSC (2.5 mM) electrode exhibited a capacitance of 300.5 F/g at a potential operating range of 1.1 V, in 0.5 M H 2 SO 4 electrolyte, and the current density of 0.5 A/g. The symmetrical supercapacitor device obtained using PPy/N-Cyclohexyl TSC (2.5 mM) electrode showed capacitance retention rate of 90.4% and 81.5% in 0.5 M H 2 SO 4 and 1.0 M Na 2 SO 4 electrolytes and at the end of the 5000 cycles life cycle test, respectively. In addition, the PPy/N-Cyclohexyl TSC (2.5 mM)/ PPy/N-Cyclohexyl TSC (2.5 mM) symmetrical supercapacitor device exhibits a specific capacitance of 175 F/g at a current density of 0.4 A/g in 0.5 M H 2 SO 4 , while 137.3 F/g in 1.0 M Na 2 SO 4 electrolyte. The energy and power density values obtained at 0.5 M H 2 SO 4 and 1.0 M Na 2 SO 4 for the supercapacitor device were 8.7 Wh/kg, 343.4 W/kg and 19.1 Wh/kg, 883.5 W/kg, respectively. • Thiosemicarbazide derivatives (TSC, N-Phenyl TSC, N-Cyclohexyl TSC) doped PPy electrode materials were obtained on PGE surface. • The PPy/N-Cyclohexyl TSC (2.5 mM) electrode exhibited a capacitance of 300.5 F/g at a potential range of 0 V - 1.1 V. • The symmetrical supercapacitor obtained using PPy/N-Cyclohexyl TSC (2.5 mM) electrode showed capacitance retention of 97%. • The energy and power density values were 8.7 Wh/kg, 343.4 W/kg at 0.5 M H2SO4, respectively. [ABSTRACT FROM AUTHOR]

A convenient and selective approach to 13,17-secoestra-1,3,5(10)-trien-17-oic acid [N'-arylcarbothioamido]hydrazides and hybrid molecules containing secosteroid and 1,2,4-triazole fragments was disclosed and these novel types of secosteroids were screened for cytotoxicity against hormone-dependent human breast cancer cell line MCF-7. Most of secosteroid–1,2,4-triazole hybrids showed significant cytotoxic effect comparable or superior to that of the reference drug cisplatin. Hit secosteroid–1,2,4-triazole hybrids 4b and 4h were characterized by high cytotoxicity and good selectivity towards MCF-7 breast cancer cells. PARP cleavage (marker of apoptosis) and ERα and cyclin D1 downregulation were discovered in MCF-7 cells treated with lead secosteroid–1,2,4-triazole hybrid 4b. The synthesized secosteroids may be considered as new promising anticancer agents. [Display omitted] • Secosteroid thiosemicarbazides and secosteroid–1,2,4-triazoles were synthesized. • A number of obtained compounds showed good cytotoxicity for MCF-7 cancer cells. • Hit compounds 4b and 4h superior to the reference drug cisplatin. • Hit compound 4b caused PARP cleavage and ERα and cyclin D1 downregulation. [ABSTRACT FROM AUTHOR]

The development of drug-resistant bacteria is currently one of the major challenges in medicine. Therefore, the discovery of novel lead structures for the design of antibacterial drugs is urgently needed. In this structure–activity relationship study, a library of ortho-, meta-, and para-fluorobenzoylthiosemicarbazides, and their cyclic analogues with 1,2,4-triazole scaffold, was created and tested for antibacterial activity against Gram-positive bacteria strains. While all tested 1,2,4-triazoles were devoid of potent activity, the antibacterial response of the thiosemicarbazides was highly dependent on substitution pattern at the N4 aryl position. The optimum activity for these compounds was found for trifluoromethyl derivatives such as 15a, 15b, and 16b, which were active against both the reference strains panel, and pathogenic methicillin-sensitive and methicillin-resistant Staphylococcus aureus clinical isolates at minimal inhibitory concentrations (MICs) ranging from 7.82 to 31.25 μg/mL. Based on the binding affinities obtained from docking, the conclusion can be reached that fluorobenzoylthiosemicarbazides can be considered as potential allosteric d-alanyl-d-alanine ligase inhibitors.

Antimicrobial resistance spurred by the overuse and misuse of antibiotics is a major global health concern, and of the Gram positive bacteria, S. aureus is a leading cause of mortality and morbidity. Alternative strategies to treat S. aureus infections, such as combination therapy, are urgently needed. In this study, a checkerboard method was used to evaluate synergistic interactions between nine thiosemicarbazides (4-benzoyl-1-(2,3-dichloro-benzoyl)thiosemicarbazides 1–5 and 4-aryl-1-(2-fluorobenzoyl)thiosemicarbazides 6–9) and conventional antibiotics against S. aureus ATCC 25923, which were determined as the fractional inhibitory concentration indices (FICIs). For these experiments, amoxicillin, gentamicin, levofloxacin, linezolid, and vancomycin were selected to represent the five antimicrobial classes most commonly used in clinical practice. With one exception of 7-vancomycin combination, none of the forty-five thiosemicarbazide-antibiotic combinations tested had an antagonistic effect, showing promising results with respect to a combination therapy. The synergic effect was observed for the 2-linezolid, 4-levofloxacin, 5-linezolid, 6-gentamicin, 6-linezolid, and 7-levofloxacin combinations. No interactions were seen in combination of the thiosemicarbazide with gentamicin or vancomycin, whereas all combinations with linezolid acted in additive or synergism, except for 6-gentamicin and 7-linezolid. The 4-(4-chlorophenyl)-1-(2-fluorobenzoyl)thiosemicarbazide 6 showed a clear preference for the potency; it affected synergistically in combinations with gentamicin or linezolid and additively in combinations with amoxicillin, levofloxacin, or vancomycin. In further studies, the inhibitory potency of the thiosemicarbazides against S. aureus DNA gyrase and topoisomerase IV was examined to clarify the molecular mechanism involved in their synergistic effect in combination with levofloxacin. The most potent synergist 6 at concentration of 100 µM was able to inhibit ~50% activity of S. aureus DNA gyrase, thereby suggesting that its anti-gyrase activity, although weak, may be a possible factor contributing to its synergism effect in combination with linezolid or gentamycin.

The Mn(II), Co(II), Ni(II) and Cu(II) complexes with two ligands derived from the addition of 2-(2-aminothiazol-5-yl) actahydrazide to ethyl (H 2 TAET) and allyl (H 2 TAAT) isothiocynates have been prepared and characterized by way of traditional strategies. The isolated complexes assigned the formulae, [Mn(HTAET) 2 (H 2 O) 2 ](2.5H 2 O), [Co(HTAET)(H 2 O) 3 Cl](2H 2 O), [Ni(HTAET)(H 2 O) 2 Cl](4H 2 O), [Mn(HTAAT)Cl](2.5H 2 O), [Co(HTAAT)(H 2 O)Cl](2H 2 O) and [Ni(HTAAT)(H 2 O)Cl]. IR data found out that the both ligands behave as monovalent bidentate via (C N) th and deprotonated enolized (C O) group in Mn(II) and Co(II) complexes of (H 2 TAET) and in all complexes of (H 2 TAAT) except Mn(II) complex. Mn(II) of (H 2 TAAT) and Ni(II) of (H 2 TAET) complexes act as monobasic tridentate (NNO) and subsequently (H 2 TAET) act as (NNS) tridentate in Cu(II) complex. The data of UV–vis spectra and the magnetic measurements recommended that the octahedral geometry for all complexes of (H 2 TAET) at the same time as tetrahedral geometry for all complexes of (H 2 TAAT) except Ni(II) that is square planar was suggested. The bond lengths, bond angles, HOMO, LUMO and dipole second values have been calculated by way of DFT the use of materials studio program to verify the recommended geometries of ligands and their metal complexes. Additionally, the kinetic and thermodynamic parameters for the different thermal degradation steps of the complexes have been decided by way of Coats-Redfern and Horowitz- Metzger techniques. The optical band gap (Eg) of the metal complexes has been calculated. The optical band gap (Eg) measurements confirmed allowed direct electronic transitions for the photon absorption inside the investigated complexes. Moreover, the antimicrobial, antioxidant and antitumor of ligands and their complexes have been evaluated. [ABSTRACT FROM AUTHOR]

New thiosemicarbazide-linked acridines 3a–c were prepared and investigated as chemosensors for the detection of biologically and environmentally important anions. The compounds 3a–c were found selective for fluoride (F−) with no affinity for other anions, i.e. −OAc, Br−, I−, HSO4−, SO42−, PO43−, ClO3−, ClO4−, CN− and SCN−. Further, upon the gradual addition of a fluoride anion (F−) source (tetrabutylammonium fluoride), a well-defined change in colour of the solution of probes 3a–c was observed. The anion-sensing process was studied in detail via UV–visible absorption, fluorescence and 1H-NMR experiments. Moreover, during the synthesis of acridine probes 3a–c nickel fluoride (NiF2), a rarely explored transition metal fluoride salt, was used as the catalyst. Theoretical studies via density functional theory were also carried out to further investigate the sensing and anion (F−) selectivity pattern of these probes.

Background: Acridine and thiourea derivatives are important compounds in medicinal chemistry due to their diverse biological properties including anticancer and antimicrobial effects. However, literature reveals some side effects associated with use of acridines. It is suggested that hybrid molecules may reduce the side effects and enhance the beneficial properties due to synergistic activity. The objectives of the present study are to synthesize and evaluate the anticancer and antimicrobial properties of new hybrids of acridine thiosemicarbazides derivatives. Results: The structures of the synthesized compounds 4a−4e were elucidated by MS and NMR spectra. In antimicrobial assay, Compound 4c exhibited potent antimicrobial activity compared to the other four compounds. In anticancer studies, we observed that compounds 4a, 4b, 4d and 4e exhibited high cytotoxicity against the MT-4 cell line, with IC50 values of 18.42 ± 1.18, 15.73 ± 0.90, 10.96 ± 0.62 and 11.63 ± 0.11 μM, respectively. The evaluation of anticancer effects, and the associated mechanism reveals that, the anticancer activities may be related to Topo I inhibitory activity, apoptosis and cell-cycle. Molecular docking studies revealed that the presence of planar naphtho-fused rings and a flexible thiourea group together, could improve DNA-intercalation and inhibition of DNA-Topo I activity. Conclusions: The results of this study demonstrate that the rational design of target derivatives as novel antimicrobial or antitumor leads is feasible.

Employing a simple synthetic protocol, a series of highly effective halogen-substituted imidazole-thiosemicarbazides with anti-Toxoplasma gondii effects against the RH tachyzoites, much better than sulfadiazine, were obtained (IC50s 10.30—113.45 µg/mL vs. ~2721.45 µg/mL). The most potent of them, 12, 13, and 15, blocked the in vitro proliferation of T. gondii more potently than trimethoprim (IC50 12.13 µg/mL), as well. The results of lipophilicity studies collectively suggest that logP would be a rate-limiting factor for the anti-Toxoplasma activity of this class of compounds.

One of the key stages in the development of new therapies in the treatment of toxoplasmosis is the identification of new non-toxic small molecules with high specificity to Toxoplasma gondii. In the search for such structures, thiosemicarbazide-based compounds have emerged as a novel and promising leads. Here, a series of imidazole-thiosemicarbazides with suitable properties for CNS penetration was evaluated to determine the structural requirements needed for potent anti-Toxoplasma gondii activity. The best 4-arylthiosemicarbazides 3 and 4 showed much higher potency when compared to sulfadiazine at concentrations that are non-toxic to the host cells, indicating a high selectivity of their anti-toxoplasma activity.