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A benzothiazole-based derivative aggregation-induced emission (AIE) fluorescent 'turn-on' probe named 2-(2-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)oxy)phenyl)benzo[d]thiazole (probe BT-BO) was developed and synthesized successfully for detecting hydrogen peroxide (H2O2) in living cells. The synthesis method of probe BT-BO is facile. Probe BT-BO demonstrates a well-resolved emission peak at 604 nm and the ability to prevent the interference of reactive oxygen species (ROS), various metal ions and anion ions, and good sensitivity. Additionally, the probe boasts impressive pH range versatility, a fast response time to H2O2 and low cytotoxicity. Finally, probe BT-BO was applied successfully to image A549 and Hep G2 cells to monitor both exogenous and endogenous H2O2. [ABSTRACT FROM AUTHOR]

The management of antibiotic-resistant, bacterial biofilm infections in skin wounds poses an increasingly challenging clinical scenario. Pseudomonas aeruginosa infection is difficult to eradicate because of biofilm formation and antibiotic resistance. In this study, we identified a new benzothiazole derivative compound, SN12 (IC 50 = 43.3 nmol/L), demonstrating remarkable biofilm inhibition at nanomolar concentrations in vitro. In further activity assays and mechanistic studies, we formulated an unconventional strategy for combating P. aeruginosa -derived infections by targeting the two-component (Gac/Rsm) system. Furthermore, SN12 slowed the development of ciprofloxacin and tobramycin resistance. By using murine skin wound infection models, we observed that SN12 significantly augmented the antibacterial effects of three widely used antibiotics—tobramycin (100-fold), vancomycin (200-fold), and ciprofloxacin (1000-fold)—compared with single-dose antibiotic treatments for P. aeruginosa infection in vivo. The findings of this study suggest the potential of SN12 as a promising antibacterial synergist, highlighting the effectiveness of targeting the two-component system in treating challenging bacterial biofilm infections in humans. Novel strategy for combating P. aeruginosa -derived infections by targeting TCSs. [Display omitted] [ABSTRACT FROM AUTHOR]

A variety of benzothiazole derivatives have been prepared via the reaction of aryl aldehydes and substituted o-amino thiophenol using nickel oxide as a nanocatalyst with an aqueous medium. By fabricating the recoverable heterogeneous nanocatalyst, the obtained nanocatalyst has been analyzed using various techniques such as powder XRD and SEM. There are some advantages of this protocol like the eco-friendly nature of the catalyst, loading of the low percentage of catalyst, good yield of products, reusability of the nanocatalyst, lesser reaction duration, high selectivity, and effortless workup. The corresponding product structures have been analyzed by the use of spectral techniques (IR, ¹H NMR, and 13C NMR) and elemental analysis. [ABSTRACT FROM AUTHOR]

A current trend in healthcare research is to discover multifunctional compounds, able to interact with multiple biological targets, in order to simplify multi-drug therapies and improve patient compliance. The aim of this work was to outline the growing demand for innovative multifunctional compounds, achieved through the synthesis, characterisation and SAR evaluation of a series of 2-styrylbenzothiazole derivatives. The six synthesised compounds were studied for their potential as photoprotective, antioxidant, antiproliferative, and anti-inflammatory agents. In order to profile antioxidant activity against various radical species, in vitro DPPH, FRAP and ORAC assays were performed. UV-filtering activity was studied, first in solution and then in formulation (standard O/W sunscreen containing 3% synthesised molecules) before and after irradiation. Compound BZTst6 proved to be photostable, suitable for broad-spectrum criteria, and is an excellent UVA filter. In terms of antioxidant activity, only compound BZTst4 can be considered a promising candidate, due to the potential of the catechol moiety. Both also showed exceptional inhibitory action against the pro-inflammatory enzyme 5-lipoxygenase (LO), with IC50 values in the sub-micromolar range in both activated neutrophils and under cell-free conditions. The results showed that the compounds under investigation are suitable for multifunctional application purposes, underlining the importance of their chemical scaffolding in terms of different biological behaviours. [ABSTRACT FROM AUTHOR]

The recent advances in the green-based design and synthesis of core-shell nanostructures have always been an intriguing arena to scientists due to their compelling application in catalytic fields. This work designed and synthesized a new core-shell nanosphere based on Fe3O4 as a novel, heterogeneous, reusable, efficient, and green catalyst to synthesize benzothiazole derivatives under ultrasonic irradiation. To achieve this goal, initially, fabricated Fe3O4 magnetic nanoparticles via the co-operation method were synthesized as a core, followed by coating with polyethylene glycol (PEG-400). Subsequently, Ni@Murexide complex supported on magnetic nanoparticles is successfully synthesized and reported, modified using 3-chloropropyltriethoxysilane (CPTES) and Murexide (MX) ligand in the Fe3O4@PEG support. The obtained structure of Fe3O4@PEG/MX/Ni was characterized by different analyses such as FT-IR, SEM, EDS, TEM, ICP-OES, XRD, VSM, and TGA. The results illustrated the effect of ultrasonic irradiation and the high efficacy of Murexide as a ligand in catalyzing the formation of benzothiazole derivatives and confirming the findings from the reaction of different derivatives of aromatic aldehyde with electron-withdrawing/donor groups with 2-amino thiophenol through a one-pot process in 10 min under ultrasonic irradiation which shows the non-sensitivity of the process to electronic effects. Furthermore, Fe3O4@PEG/MX@Ni showed great use at least six times with no significant loss in catalyst activity. [ABSTRACT FROM AUTHOR]

In this study, a semi-static water exposure method was employed to investigate the early developmental and neurotoxic effects of four benzothiazole substances (BTHs), namely benzothiazole (BTH), 2-mercaptobenzothiazole (MBT), 2-hydroxybenzothiazole (BTON), and 2-aminobenzothiazole (2-ABTH), on zebrafish at an equimolar concentration of 10 μM. The findings revealed that all four BTHs exerted certain impacts on early development in zebrafish. MBT stimulated spontaneous movement in juvenile zebrafish, whereas BTON inhibited such movements. Moreover, all four BTHs hindered the hatching process of zebrafish larvae, with MBT exhibiting the strongest inhibition at 24 h post-fertilization (hpf). Notably, MBT acted as a melanin inhibitor by suppressing melanin production in juvenile zebrafish eyes and weakening phototaxis. Additionally, both BTH and BTON exhibited significantly lower speeds than the control group and other test groups under conditions without bright field stimulation; however, their speeds increased to average levels after percussion stimulation, indicating no significant alteration in motor ability among experimental zebrafish groups. Short-term exposure to these four types of BTHs induced oxidative damage in zebrafish larvae; specifically, BTH-, MBT-, and BTON-exposed groups displayed abnormal expression patterns of genes related to oxidative damage. Exposure to both BTH and MBT led to reduced fluorescence intensity in transgenic zebrafish labeled with central nervous system markers, suggesting inhibition of central nervous system development. Furthermore, real-time quantitative PCR results demonstrated abnormal gene expression associated with neural development. However, no significant changes were observed in 2-ABTH gene expression at this concentration. Overall findings indicate that short-term exposure to BTHs stimulates neurodevelopmental gene expression accompanied by oxidative damage. [ABSTRACT FROM AUTHOR]

Introduction: Cancer, a significant global health concern, necessitates innovative treatments. The pivotal role of chronic inflammation in cancer development underscores the urgency for novel therapeutic strategies. Benzothiazole derivatives exhibit promise due to their distinctive structures and broad spectrum of biological effects. This study aims to explore new anti-tumor small molecule drugs that simultaneously anti-inflammatory and anticancer based on the advantages of benzothiazole frameworks. Methods: The compounds were characterized by nuclear magnetic resonance (NMR), liquid chromatograph-mass spectrometer (LC-MS) and high performance liquid chromatography (HPLC) for structure as well as purity and other related physicochemical properties. The effects of the compounds on the proliferation of human epidermoid carcinoma cell line (A431) and human non-small cell lung cancer cell lines (A549, H1299) were evaluated by MTT method. The effect of compounds on the expression levels of inflammatory factors IL-6 and TNF-α in mouse monocyte macrophages (RAW264.7) was assessed using enzyme-linked immunosorbent assay (ELISA). The effect of compounds on apoptosis and cell cycle of A431 and A549 cells was evaluated by flow cytometry. The effect of compounds on A431 and A549 cell migration was evaluated by scratch wound healing assay. The effect of compounds on protein expression levels in A431 and A549 cells was assessed by Western Blot assay. The physicochemical parameters, pharmacokinetic properties, toxicity and drug similarity of the active compound were predicted using Swiss ADME and admetSAR web servers. Results: Twenty-five novel benzothiazole compounds were designed and synthesized, with their structures confirmed through spectrogram verification. The active compound 6-chloro-N-(4-nitrobenzyl) benzo[d] thiazol-2-amine (compound B7) was screened through a series of bioactivity assessments, which significantly inhibited the proliferation of A431, A549 and H1299 cancer cells, decreased the activity of IL-6 and TNF-α, and hindered cell migration. In addition, at concentrations of 1,2, and 4 μM, B7 exhibited apoptosis-promoting and cell cycle-arresting effects similar to those of the lead compound 7-chloro-N-(2, 6- dichlorophenyl) benzo[d] thiazole-2-amine (compound 4i). Western blot analysis confirmed that B7 inhibited both AKT and ERK signaling pathways in A431 and A549 cells. The prediction results of ADMET indicated that B7 had good drug properties. Discussion: This study has innovatively developed a series of benzothiazole derivatives, with a focus on compound B7 due to its notable dual anticancer and anti-inflammatory activities. B7 stands out for its ability to significantly reduce cancer cell proliferation in A431, A549, and H1299 cell lines and lower the levels of inflammatory cytokines IL-6 and TNF-α. These results position B7B7 as a promising candidate for dual-action cancer therapy. The study's mechanistic exploration, highlighting B7's simultaneous inhibition of the AKT and ERK pathways, offers a novel strategy for addressing both the survival mechanisms of tumor cells and the inflammatory milieu facilitating cancer progression. [ABSTRACT FROM AUTHOR]

A current trend in healthcare research is to discover multifunctional compounds, able to interact with multiple biological targets, in order to simplify multi-drug therapies and improve patient compliance. The aim of this work was to outline the growing demand for innovative multifunctional compounds, achieved through the synthesis, characterisation and SAR evaluation of a series of 2-styrylbenzothiazole derivatives. The six synthesised compounds were studied for their potential as photoprotective, antioxidant, antiproliferative, and anti-inflammatory agents. In order to profile antioxidant activity against various radical species, in vitro DPPH, FRAP and ORAC assays were performed. UV-filtering activity was studied, first in solution and then in formulation (standard O/W sunscreen containing 3% synthesised molecules) before and after irradiation. Compound BZTst6 proved to be photostable, suitable for broad-spectrum criteria, and is an excellent UVA filter. In terms of antioxidant activity, only compound BZTst4 can be considered a promising candidate, due to the potential of the catechol moiety. Both also showed exceptional inhibitory action against the pro-inflammatory enzyme 5-lipoxygenase (LO), with IC50 values in the sub-micromolar range in both activated neutrophils and under cell-free conditions. The results showed that the compounds under investigation are suitable for multifunctional application purposes, underlining the importance of their chemical scaffolding in terms of different biological behaviours.

'Albedo bluing' of fruits occurs in many varieties of citrus, resulting in a significant reduction in their commercial value. We first presented a breakthrough method for successfully extracting and purifying the 'albedo bluing' substance (ABS) from citrus fruits, resulting in the attainment of highly purified ABS. Then, HPLC and UPLC-QTOF-MS were used to prove that ABS in the fruits of three citrus varieties (Citrus reticulate Blanco cv. 'Gonggan', 'Orah', and 'Mashuiju') are identical. However, the chemical structure of ABS remains elusive for many reasons. Fortunately, a more stable derivative of ABS (ABS-D) was successfully obtained. Through various analytical techniques such as HRESIMS, 1D and 2D NMR, and chemical shift calculation, ABS-D was identified as 2,4-dihydroxy-6-(β-D-glucopyranosyloxy)phenyl(5,6-dihydroxy-7-(β-D-glucopyranosyloxy)benzo[d]thiazol-2-yl)methanone, indicating that both ABS and its derivative belong to a rare category of benzothiazole glucosides. Furthermore, both ABS and ABS-D demonstrated potent antioxidant abilities. These findings lay the groundwork for further elucidating the chemical structure of ABS and the causative mechanism of the 'albedo bluing' phenomenon in citrus fruits. [ABSTRACT FROM AUTHOR]

In this study, new benzothiazole–pyrimidine hybrids (5a–c, 6, 7a–f, and 8–15) were designed and synthesised. Two different functionalities on the pyrimidine moiety of lead compound 4 were subjected to a variety of chemical changes with the goal of creating various functionalities and cyclisation to further elucidate the target structures. The potency of the new molecules was tested against different tuberculosis (TB) strains. The results indicated that compounds 5c, 5b, 12, and 15 (MIC = 0.24–0.98 µg/mL) are highly active against the first-line drug-sensitive strain of Mycobacterium tuberculosis (ATCC 25177). Thereafter, the anti-tubercular activity was evaluated against the two drug-resistant TB strains; ATCC 35822 and RCMB 2674, where, many compounds exhibited good activity with MIC = 0.98–62.5 3 µg/mL and 3.9–62.5 µg/mL, respectively. Compounds 5c and 15 having the highest anti-tubercular efficiency towards sensitive strain, displayed the best activity for the resistant strains by showing the MIC = 0.98 and 1.95 µg/mL for MDR TB, and showing the MIC = 3.9 and 7.81 µg/mL for XDR TB, consecutively. Finally, molecular docking studies were performed for the two most active compounds 5c and 15 to explore their enzymatic inhibitory activities. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases such as Alzheimer's disease (AD) are multifactorial with several different pathologic mechanisms. Therefore, it is assumed that multitargeted-directed ligands (MTDLs) which interact with different biological targets relevant to the diseases, might offer an improved therapeutic alternative than using the traditional "one-target, one-molecule" approach. Herein, we describe new benzothiazole-based derivatives as a privileged scaffold for histamine H3 receptor ligands (H3R). The most affine compound, the 3-(azepan-1-yl)propyloxy-linked benzothiazole derivative 4b, displayed a Ki value of 0.012 μM. The multitargeting potential of these H3R ligands towards AChE, BuChE and MAO-B enzymes was evaluated to yield compound 3s (pyrrolidin-1-yl-(6-((5-(pyrrolidin-1-yl)pentyl)oxy)benzo[d]thiazol-2-yl)methanone) as the most promising MTDL with a Ki value of 0.036 μM at H3R and IC50 values of 6.7 µM, 2.35 µM, and 1.6 µM towards AChE, BuChE, and MAO-B, respectively. These findings suggest that compound 3s can be a lead structure for developing new multi-targeting anti-AD agents. [ABSTRACT FROM AUTHOR]

To discover novel multifunctional agents for the treatment of Parkinson's disease, a series of 2-(4-(benzyloxy)-5-(hydroxyl) phenyl) benzothiazole derivatives was designed, synthesized and evaluated. The results revealed that representative compound 3h possessed potent and selective MAO-B inhibitory activity (IC50 = 0.062 µM), and its inhibitory mode was competitive and reversible. Additionally, 3h also displayed excellent anti-oxidative effect (ORAC = 2.27 Trolox equivalent), significant metal chelating ability and appropriate BBB permeability. Moreover, 3h exhibited good neuroprotective effect and anti-neuroinflammtory ability. These results indicated that compound 3h was a promising candidate for further development against PD. [ABSTRACT FROM AUTHOR]

The benzothiazole nucleus is a major heterocyclic scaffold whose therapeutic potential has been thoroughly explored due to its structural simplicity and ease of synthesis. In fact, several benzothiazole derivatives have been synthesized over time, demonstrating numerous pharmacological properties such as anticancer, antimicrobial, anti-inflammatory, and antioxidant activities. Herein, we propose a new series of benzothiazole-phthalimide hybrids obtained by linking the phthalimide moiety to differently substituted benzothiazole nuclei through the N atom. These compounds have been screened for their anticancer properties against two human breast cancer cell lines. Furthermore, we delved into the mechanism of action of the most active hybrid, compound 3h, by assessing its capability to damage the nuclear DNA, trigger the apoptotic process in the high metastatic MDA-MB-231 cells, and prevent cellular migration. Moreover, in view of the documented antimicrobial activities of the two scaffolds involved, we explored the antibacterial and antifungal effects of the studied compounds by means of the broth microdilution method. Among the studied compounds, 3h showed the highest antimicrobial activity, both against gram-positive and gram-negative bacterial strains belonging to the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) and against fungal strains of the Candida species with MICs values ranging from 16 to 32 µg/mL. [ABSTRACT FROM AUTHOR]

In recent years, the development of photocatalysts based on noncovalent strategies has shown an important role in medical and organic materials. Herein, an organic fluorescent dye benzothiazole derivative (2‐(N,N‐diethylanilin‐4‐yl)‐4,6‐bis(3‐methylpyrazol‐1‐yl)‐1,3,5‐triazine [MPBT]) was designed and synthesized. It was encapsulated in the cavity of cucurbit[8]uril (CB[8]) to form a supramolecular dimer through host–guest interaction, which converted the dye into a highly efficient photocatalyst. With the formation of 2MPBT‐CB[8] supramolecular dimer, the emergence of host‐enhanced charge transfer interactions could significantly facilitate singlet to triplet through intersystem crossing. At the same time, the alternating structure of 2MPBT‐CB[8] facilitated the triplet states for further energy transfer and electron transfer. In addition, the electron transfer process with electron donor generated cationic free radical and photocatalyst negative ion free radical (PC⋅− ${\text{PC}}^{\cdot -}$), which in turn reacted with oxygen (O2) to form superoxide anion radical (O2⋅− ${{\rm{O}}}_{2}^{\cdot -}$). The generated O2⋅− ${{\rm{O}}}_{2}^{\cdot -}$ could be used to catalyze the oxidative hydroxylation of aryl boronic acid. Therefore, the 2MPBT‐CB[8] had become a highly efficient photocatalyst for the oxidative hydroxylation of aryl boronic acid. This strategy of supramolecular dimerization provides a new strategy for the development of new photocatalysts based on noncovalent interactions. [ABSTRACT FROM AUTHOR]

Herein, we have reported the facile synthesis of various benzimidazole/benzothiazole by using DBU-iodine-iodide as a green and simple catalyst. The R3NHI3 complexes have been formed by reacting an aqueous mixture of ammonium iodide and molecular iodine with the aqueous solution of amine. The structure of R3NHI3 complexes has been confirmed by spectroscopic techniques. The prepared amine-iodine complexes were screened as a catalysts in the synthesis of benzimidazole/benzothiazoles. Among the screened catalysts DBUHI3 complex has been found as most efficient catalyst. The synthesis of benzimidazoles and benzothiazoles has been achieved with the reaction of ophenylene diamine/o-aminothiophenol and various substituted aryl aldehyde using DBUHI3 as a catalyst. The present protocol has offered some advantages over other reported protocols such as the mild reaction condition, commercially available precursors, inexpensive catalyst, short reaction time, the broad scope of the substrate, high yield, simple isolation of the product and environmentally benign method. [ABSTRACT FROM AUTHOR]

Apoptosis plays a crucial role in cancer pathogenesis and drug resistance. BCL-2 family of enzymes is considered as one of the key enzymes which is involved in apoptosis. When there is disruption in the balance between anti-apoptotic and pro-apoptotic members of the BCL-2 family apoptosis is dysregulated in the affected cells. Herein, 33 novel benzothiazole-based molecules 7a-i, 8a-f, 9a-b, 12a-e, 13a-d, 14a,b, and 17a-j were designed, synthesized and tested for their BCL-2 inhibitory activity. Scaffold hopping strategy was applied in designing of the target compounds. Compounds 13c and 13d showed the highest activity with IC50 values equal to 0.471 and 0.363 µM, respectively. Molecular docking studies of the synthesized compounds showed comparable binding interactions with the lead compound. Structure activity relationship study was performed to show the effects of structural modifications on the inhibitory activities on BCL-2. [ABSTRACT FROM AUTHOR]

This study describes the synthesis of 2,5-Bis(3,4-dialkoxy phenyl) Thiazolo[5,4-d} thiazoles (DAITn) (I) and its subsequent structural analysis. These compounds were prepared via reaction of dithio-oxarnidc with the freshly prepared 3,4-dialkoxy benzaldehyde in (DMF). The structure of DAITn (I) was found to have the 3 and 4 positions of the two benzene rings substituted with (OCnH2n+h n=2-5) which equaled to compound M2-M5. The primary methods used for theoretical calculations in this study are quantum mechanics/molecular dynamics simulations based on Density Functional Theory (DFT) and Monte Carlo. The Gaussian09W software's B3LYP hybrid feature and 6-311++G(d,p) basis set were employed in both the gas and aqueous phase for protonated and non-protonated species at the B3LYP level. Electronic structural identifiers were discovered from geometryoptimized structures and correlations between EHOMO (higher occupied molecular orbital energy), ELUMO (lower unoccupied molecular orbital energy), (Eg) bandgap energy, (I) ionization energy, (χ) electronegativity, (ΔN) electron transfer, and (ΔE_(b-d)) back-donation energy were calculated. The Monte Carlo method was used to calculate the adsorption for all identified compounds in this study, and a Fe (110) crystal more stable surface was selected. UV-visible spectroscopy is measuring absorption coefficient, transmittance, and electrical conductivity, and uses a Tauc plot for bandgap energy of the highest absorption peaks. ADTTn molecules with a wide bandgap and a high optical conductivity. Thermodynamic parameters, molecular dynamics simulations, and adsorption energy have been examining inhibitor/surface interactions with greater binding energy leading to stronger interaction and larger negative adsorption energy value indicating a more stable interaction. A four-slab model featuring eighty iron atoms per layer, or one hundred- and ten-unit cells, was used, along with a spline transformation function and a cut-off distance of 1.85 nm for nonbonded interactions. Simulated heating was employed to progressively lower the temperature and search for a low-energy adsorption site. [ABSTRACT FROM AUTHOR]

In this work, we focused on synthesizing and assessing novel chitosan-based antibacterial polymers and their nanoparticles by incorporating benzothiazole substituents. The growing resistance to antibiotics has necessitated the search for alternative antimicrobial compounds. This study aimed to synthesize and evaluate chitosan-based polymers and nanoparticles with benzothiazole substituents for their antibacterial properties and toxicity. The benzothiazole derivatives of chitosan and their nanoparticles were synthesized through electrochemical coupling. The in vivo antibacterial efficacy was tested on white rats with induced peritonitis using a microbial suspension containing S. aureus and E. coli. Additionally, in vitro and in vivo toxicity assessments were conducted. The chitosan-based antibacterial systems showed significant in vivo antibacterial activity, surpassing that of unmodified chitosan and commercial antibiotics. Moreover, the toxicity studies revealed low toxicity levels of the synthesized derivatives, which did not differ significantly from native chitosan. The synthesized chitosan-based polymers and nanoparticles demonstrated potent antibacterial activity and low toxicity, highlighting their potential as effective alternatives to traditional antibiotics. Further investigations in pharmacology and preclinical trials are recommended to explore their application in clinical settings. [ABSTRACT FROM AUTHOR]

In this research, the synthesis of piperazine immobilized on nano-ZnO-sulfuric acid (PINZS) as a new piperazine-based nano-reagent is reported. After identification of PINZS using different techniques including XRD (X-ray powder diffraction), TGA (thermogravimetric analysis), FT-IR (Fourier transform infrared spectroscopy), FESEM (field emission scanning electron microscopy), and EDX (energy-dispersive X-ray) analysis, this reagent is efficiently used for the synthesis of 1-(benzothiazolylamino) phenylmethyl-2-naphthols and pyrimido[1, 2-a]benzimidazoles via a domino Knoevenagel/Michael sequence which identified acceptable reaction times (7–45 min.), great yields (up to 98%) and ease of the preparation, separation, and recovery of PINZS (for three times) as the most important features of this protocol. Use of PINZS in the synthesis of some important heterocycles. [ABSTRACT FROM AUTHOR]

Benzoxazole and benzothiazole have a broad spectrum of agricultural biological activities, such as antibacterial, antiviral, and herbicidal activities, which are important fused heterocyclic scaffold structures in agrochemical discovery. In recent years, great progress has been made in the research of benzoxazoles and benzothiazoles, especially in the development of herbicides and insecticides. With the widespread use of benzoxazoles and benzothiazoles, there may be more new products containing benzoxazoles and benzothiazoles in the future. We systematically reviewed the application of benzoxazoles and benzothiazoles in discovering new agrochemicals in the past two decades and summarized the antibacterial, fungicidal, antiviral, herbicidal, and insecticidal activities of the active compounds. We also discussed the structural–activity relationship and mechanism of the active compounds. This work aims to provide inspiration and ideas for the discovery of new agrochemicals based on benzoxazole and benzothiazole. [ABSTRACT FROM AUTHOR]

Spinal cord hemisection at C2 (C2SH), sparing the dorsal column is widely used to investigate the effects of reduced phrenic motor neuron (PhMN) activation on diaphragm muscle (DIAm) function, with reduced DIAm activity on the injured side during eupnoea. Following C2SH, recovery of DIAm EMG activity may occur spontaneously over subsequent days/weeks. Various strategies have been effective at improving the incidence and magnitude of DIAm recovery during eupnoea, but little is known about the effects of C2SH on transdiaphragmatic pressure (Pdi) during other ventilatory and non‐ventilatory behaviours. We employ SPG302, a novel type of pegylated benzothiazole derivative, to assess whether enhancing synaptogenesis (i.e., enhancing spared local connections) will improve the incidence and the magnitude of recovery of DIAm EMG activity and Pdi function 14 days post‐C2SH. In anaesthetised Sprague‐Dawley rats, DIAm EMG and Pdi were assessed during eupnoea, hypoxia/hypercapnia and airway occlusion prior to surgery (C2SH or sham), immediately post‐surgery and at 14 days post‐surgery. In C2SH rats, 14 days of DMSO (vehicle) or SPG302 treatments (i.p. injection) occurred. At the terminal experiment, maximum Pdi was evoked by bilateral phrenic nerve stimulation. We show that significant EMG and Pdi deficits are apparent in C2SH compared with sham rats immediately after surgery. In C2SH rats treated with SPG302, recovery of eupneic, hypoxia/hypercapnia and occlusion DIAm EMG was enhanced compared with vehicle rats after 14 days. Treatment with SPG302 also ameliorated Pdi deficits following C2SH. In summary, SPG302 is an exciting new therapy to explore for use in spinal cord injuries. Key points: Despite advances in our understanding of the effects of cervical hemisection (C2SH) on diaphragm muscle (DIAm) EMG activity, very little is understood about the impact of C2SH on the gamut of ventilatory and non‐ventilatory transdiaphragmatic pressures (Pdi).Recovery of DIAm activity following C2SH is improved using a variety of approaches, but very few pharmaceuticals have been shown to be effective. One way of improving DIAm recovery is to enhance the amount of latent local spared connections onto phrenic motor neurons. A novel pegylated benzothiazole derivative enhances synaptogenesis in a variety of neurodegenerative conditions.Here, using a novel therapeutic SPG302, we show that 14 days of treatment with SPG302 ameliorated DIAm EMG and Pdi deficits compared with vehicle controls.Our results show that SPG302 is a compound with very promising potential for use in improving functional outcomes post‐spinal cord injury. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is one of the most common malignancies causing the third highest mortality rate in the world. It is particularly urgent to explore effective therapeutic strategies to overcome this disease. We identified a novel benzothiazole derivative (BTD) that may serve as a potentially effective agent against CRC. Method: MTT assays, cell colony formation assays, EdU staining assays, flow cytometry, RNA-seq, Western blotting, and migration and invasion assays were used to examine the effects of BTD on cell proliferation, apoptosis, metastasis, and the cell cycle, The antitumor activity of BTD in vivo was investigated in a CT26 tumor-bearing mouse model, Immunohistochemistry (IHC) was performed to examine the protein expression in mouse tumors, Hematology, biochemical analysis, and H&E staining were used to assess the biosafety of BTD. Results: We observed that BTD suppressed cell proliferation and metastasis and promoted the apoptosis of tumor cells in vitro, Treatment with BTD at a tolerable dose significantly reduced tumor growth in CT26-tumor-bearing mice and appeared to be safe, Treatment of BTD induced apoptosis by increasing the generation of reactive oxygen species (ROS) and evoking the loss of mitochondrial transmembrane potential, Overall, BTD suppressed cell proliferation and metastasis, and induced apoptosis of colorectal tumor cells through the ROS-mitochondria-mediated apoptotic pathway, The preliminary proof of the antitumor activity and relative safety of BTD were validated in a mouse model. Conclusion: Our findings suggest that BTD could serve as a potentially safe and effective candidate for CRC treatment. [ABSTRACT FROM AUTHOR]

Amoebiasis is produced by the parasite Entamoeba histolytica; this disease affects millions of people throughout the world who may suffer from amoebic colitis or amoebic liver abscess. Metronidazole is used to treat this protozoan, but it causes important adverse effects that limit its use. Studies have shown that riluzole has demonstrated activity against some parasites. Thus, the present study aimed, for the first time, to demonstrate the in vitro and in silico anti-amoebic activity of riluzole. In vitro, the results of Entamoeba histolytica trophozoites treated with IC50 (319.5 μM) of riluzole for 5 h showed (i) a decrease of 48.1% in amoeba viability, (ii) ultrastructural changes such as a loss of plasma membrane continuity and alterations in the nuclei followed by lysis, (iii) apoptosis-like cell death, (iv) the triggering of the production of reactive oxygen species and nitric oxide, and (v) the downregulation of amoebic antioxidant enzyme gene expression. Interestingly, docking studies have indicated that riluzole presented a higher affinity than metronidazole for the antioxidant enzymes thioredoxin, thioredoxin reductase, rubrerythrin, and peroxiredoxin of Entamoeba histolytica, which are considered as possible candidates of molecular targets. Our results suggest that riluzole could be an alternative treatment against Entamoeba histolytica. Future studies should be conducted to analyze the in vivo riluzole anti-amoebic effect on the resolution of amebic liver abscess in a susceptible model, as this will contribute to developing new therapeutic agents with anti-amoebic activity. [ABSTRACT FROM AUTHOR]

(Thio)ureas ((T)Us) and benzothiazoles (BTs) each have demonstrated to have a great variety of biological activities. When these groups come together, the 2-(thio)ureabenzothizoles [(T)UBTs] are formed, improving the physicochemical as well as the biological properties, making these compounds very interesting in medicinal chemistry. Frentizole, bentaluron and methabenzthiazuron are examples of UBTs used for treatment of rheumatoid arthritis and as wood preservatives and herbicides in winter corn crops, respectively. With this antecedent, we recently reported a bibliographic review about the synthesis of this class of compounds, from the reaction of substituted 2-aminobenzothiazoles (ABTs) with iso(thio)cyanates, (thio)phosgenes, (thio)carbamoyl chlorides, 1,1'-(thio)carbonyldiimidazoles, and carbon disulfide. Herein, we prepared a bibliographic review about those features of design, chemical synthesis, and biological activities relating to (T)UBTs as potential therapeutic agents. This review is about synthetic methodologies generated from 1968 to the present day, highlighting the focus to transform (T)UBTs to compounds containing a range substituents, as illustrated with 37 schemes and 11 figures and concluded with 148 references. In this topic, the scientists dedicated to medicinal chemistry and pharmaceutical industry will find useful information for the design and synthesis of this interesting group of compounds with the aim of repurposing these compounds. [ABSTRACT FROM AUTHOR]

Herein, the synthesis, structural characterization and in vitro biological evaluation of a novel Cu(II) complex with the 2-(4-aminophenyl)benzothiazole pharmacophore conjugated with the (2-pyridinyl)methylamino chelating moiety is reported for the first time. A full characterization of the Cu(II) complex was conducted by X-ray crystallography, EPR, IR, elemental and MS analysis, and its binding to CT-DNA was investigated by UV-vis spectroscopy, ethidium bromide competition studies, circular dichroism, viscometry and thermal denaturation. The data clearly indicate that the Cu(II) complex interacts with CT-DNA via intercalation, registering a difference compared to previously reported Pt(II) and Pd(II) analogues. To evaluate the anticancer activity of the complex, a series of in vitro experiments against breast, glioblastoma, prostate and lung cancer cell lines along with healthy fibroblasts were implemented. Cytotoxicity, cellular uptake, intracellular ROS production, cell cycle and apoptosis analysis revealed an increased anticancer activity towards breast cancer cells that is accompanied by an induction in intracellular ROS levels and a significant G2/M arrest followed by apoptosis. [ABSTRACT FROM AUTHOR]

Mild steel surfaces were coated with four different benzothiazole derivatives with long alkyl chain, namely 2-(heptyl)-benzothiazole (HEBT), 2-(tridecyl)-benzothiazole (TDBT), 2- (pentadecyl)-benzothiazole (PDBT), and 2-(heptadec-8-en-1-yl)benzothiazole (HDBT) from their respective chloroform solutions. Electrochemical experiments were conducted with coated and uncoated mild steel samples exposed to 1 M aqueous HCl at temperatures between 20°C to 50°C and at different immersion times from 6 h to 48 h. TDBT behaves as the best corrosion inhibitor among the four (more than 99 % efficiency at 40°C) and the order of inhibition efficiency follows the trend: TDBT>HDBT>PDBT>HEBT. This reflects the inhibition efficiency to increase with chain length initially, but decreases after a threshold. HDBT, in-spite of having longest aliphatic chain, exhibits better inhibitory performance over PDBT. This is attributed to the presence of unsaturation in HDBT. TDBT coating maintains high corrosion inhibition efficiency even after the 24 h of exposure (above 98 %). Occurrence of spatial hindrance during adsorption of BT derivatives with long aliphatic chain has been manifested by MD simulation. [Display omitted] • Benzothiazole coupled with long aliphatic chain is coated on mild steel. • Electrochemical property of the coated mild steel is assessed in aqueous HCl. • Coated mild steel surface is analysed by XPS and SEM. • Aliphatic chain length and unsaturation in the chain affects inhibitory performance. • MD simulation shows spatial hindrance for long chain molecules affecting adsorption. [ABSTRACT FROM AUTHOR]

[Display omitted] • A bifunctional probe was devised for the detection of HSO 3 −/SO 3 2− and viscosity. • HFBT shows excellent spectral response to HSO 3 −/SO 3 2− and viscosity. • HFBT achieves ratiometric fluorescence and colorimetric detection of HSO 3 −/SO 3 2−. • HFBT can be used for the detection of HSO 3 −/SO 3 2− in food samples. • HFBT has large Stokes shift and high resonance energy transfer efficiency. Sulfur dioxide (SO 2) and viscosity play important roles in living organisms, and abnormal levels of them are associated with many diseases. Hence, a bifunctional fluorescence probe (E)-3-(2-(4-(4-(4-(6-fluoro-3-hydroxy-4-oxo-4 H -chromen-2-yl)benzoyl)piperazin-1-yl)styryl)benzo-[d]thiazol-3-ium-3-yl)propane-1-sulfonate (HFBT) with fluorescence resonance energy transfer (FRET) properties was successfully constructed by using 3-hydroxyflavonol as the energy donor and benzothiazole sulphonate derivatives as the energy acceptor, and it can be used for the detection of SO 2 derivatives (HSO 3 −/HSO 3 2−) and viscosity. HFBT exhibits a large Stokes shift (245 nm), high resonance energy transfer efficiency (95.56 %), and excellent selectivity, anti-interference and low limit of detection (LOD = 0.057 μM) for HSO 3 −. The fluorescence intensity of HFBT at 596 nm gradually increases with the increase of viscosity. Interestingly, a visual HSO 3 − detection platform was successfully constructed and applied to the quantitative detection of HSO 3 − in food. Additionally, HFBT was successfully applied to imaging endogenous and exogenous HSO 3 − in cells. The successful development of HFBT provides an effective tool for the detection and imaging of HSO 3 − in food and cells. [ABSTRACT FROM AUTHOR]

• The photoactive benzobisoxazole-containing COF was successfully constructed. • The resultant COF material exhibited high crystallinity, chemical stability, and outstanding photophysical properties. • The catalyst system exhibited high photocatalytic activity, excellent stability and recyclability. • The photocatalytic mechanism of COF catalyst was extensively investigated. • The results also demonstrate the potential of COFs for practical applications. Covalent organic frameworks, as an emerging porous crystalline material, have attracted significant interest in heterogeneous photocatalysis, due to their tunable structure, large specific surface area, high chemical stability, and extendable π-conjugated skeleton. In this study, 4,4′-(2,6-dimethylbenzo[1,2-d:4,5-d′]bis(oxazolyl)-4,8-diyl)dianiline (OZDL) and benzene-1,3,5-tricarboxaldehyde (BTCA) were utilized to construct 2D covalent organic frameworks OZBT-COF through aldehyde-amine polycondensation reaction under solvothermal conditions. Considering the high crystallinity, chemical stability, and outstanding photophysical properties, the benzobisoxazole-containing OZBT-COF was further employed as a photocatalyst for the synthesis of the benzothiazole derivatives and the oxidation of N-substituted tetrahydroisoquinolines. The catalyst system exhibited high photocatalytic activity, moderate substrate applicability, excellent stability and recyclability. The suitable band gap, efficient separation of photogenerated charge carriers, and enhancing mass transport inside the porous catalyst could be contributed to superior photocatalytic performance. This work provides valuable insights into the structure–function correlations of COFs-based photocatalysts, and further demonstrates promising opportunities for developing COF photocatalysts with practical applications. [ABSTRACT FROM AUTHOR]

A current trend of research in the health field is toward the discovery of multifunctional compounds, capable of interacting with multiple biological targets, thus simplifying multidrug therapies and improving patient compliance. The aim of this work was to synthesize new multifunctional chemical entities bearing a benzothiazole nucleus, a structure that has attracted increasing interest for the great variety of biological actions that it can perform, and already used as a scaffold in several multifunctional drugs. Compounds are reported, divided into two distinct series, synthetized and tested in vitro for the antioxidant, and include UV-filtering and antitumor activities. DPPH and FRAP tests were chosen to outline an antioxidant activity profile against different radical species. The UV-filtering activity was investigated, pre- and post-irradiation, through evaluation of a O/W sunscreen standard formulation containing 3% of the synthetic compounds. The antitumor activity was investigated both on human melanoma cells (Colo-38) and on immortalized human keratinocytes as a control (HaCat). A good antiproliferative profile in terms of IC50 was chosen as a mandatory condition to further investigate apoptosis induction as a possible cytotoxicity mechanism through the Annexin V test. Compound BZTcin4 was endowed with excellent activity and a selectivity profile towards Colo-38, supported by a good antioxidant capacity and an excellent broad-spectrum photoprotective profile. [ABSTRACT FROM AUTHOR]

Bidentate ligand (L) was synthesized by knoevenagel reaction using 4-bromobenzaldehyde and 2-amino-6- methylbenzothiazole. The ligand has been confirmed from the analytical technique such as UV-Vis, FTIR, NMR, Mass and EPR spectral. The synthesized metal complexes were characterized from the spectra and physico-chemical techniques. These studies showed that the stoichiometric composition of ML2 type complexes. Absorption study implies that the compounds possess the octahedral geometry and their chelates are electrolytic and monomeric in nature. Absorption and gel electrophoresis experiments set up accepted the effective interaction with CT-DNA molecules. It was extended to Fluorescence emission study of binding. The anti-bacterial and antifungi studies were carried out by disc diffusion method. From the MIC values, metal complexes were controlling larger than Schiff base. [ABSTRACT FROM AUTHOR]

A series of new benzothiazole-derived donor–acceptor-based compounds (Comp1–4) were synthesized and characterized with the objective of tuning their multifunctional properties, i.e., charge transport, electronic, and optical. All the proposed structural formulations (Comp1–4) were commensurate using FTIR, 1H NMR, 13C NMR, ESI-mass, UV–vis, and elemental analysis techniques. The effects of the electron-donating group (-CH3) and electron-withdrawing group (-NO2) on the optoelectronic and charge transfer properties were studied. The substituent effect on absorption was calculated at the TD-B3LYP/6-31+G** level in the gas and solvent phases. The effect of solvent polarity on the absorption spectra using various polar and nonpolar solvents, i.e., ethanol, acetone, DMF, and DMSO was investigated. Light was shed on the charge transport in benzothiazole compounds by calculating electron affinity, ionization potential, and reorganization energies. Furthermore, the synthesized compounds were used to prepare thin films on the FTO substrate to evaluate the charge carrier mobility and other related device parameters with the help of I-V characteristic measurements. [ABSTRACT FROM AUTHOR]

A new series of 1,2,3-triazole derivatives 5a–f based on benzothiazole were synthesized by the 1,3-dipolar cycloaddition reaction of S-propargyl mercaptobenzothiazole and α-halo ester/amide in moderate to good yields (47–75%). The structure of all products was characterized by 1H NMR, 13C NMR, and CHN elemental data. This protocol is easy and green and proceeds under mild and green reaction conditions with available starting materials. The structural and electronic analysis and 1H and 13C chemical shifts of the characterized structure of 5e were also calculated by applying the B3LYP/6-31 + G(d, p) level of density functional theory (DFT) method. In the final section, all the synthesized compounds were evaluated for their anti-inflammatory activity by biochemical COX-2 inhibition, antifungal inhibition with CYP51, anti-tuberculosis target protein ENR, DPRE1, pks13, and Thymidylate kinase by molecular docking studies. The ADMET analysis of the molecules 5a–f revealed that 5d and 5a are the most-promising drug-like molecules out of the six synthesized molecules. [ABSTRACT FROM AUTHOR]

The drug-resistance problem is widely spread and becoming more common in community-acquired and nosocomial strains of bacteria. Therefore, finding new antimicrobial agents remains an important drug target. From this perspective, new derivatives of benzothiazole were synthesized and evaluated for their antimicrobial activity and ability to inhibit the DHPS enzyme. The synthesis was carried out by the reaction of benzothiazole N-arylsulphonylhydrazone with N-aryl-2-cyano-3-(dimethylamino)acrylamide, N-aryl-3-(dimethylamino)prop-2-en-1-one, arylaldehydes or diazonium salt of arylamine derivatives, which led to the formation of N-arylsulfonylpyridones 6a–d (yield 60–70%) and 12a–c (yield 50–60%),N-(2-(benzo[d]thiazole-2-yl)-3-arylacryloyl-4-methylsulfonohydrazide 14a–c (yield 60–65%), 4-(benzo[d]thiazole-2-yl)-5-aryl-1H-pyrazol-3(2H)-one 16a–c (yield 65–75%), and N′-(2-(benzo[d]thiazol-2-yl)-2-(2-arylhydrazono)acetyl)-4-arylsulfonohydrazide 19a–e (yield 85–70%). The antimicrobial evaluations resulted into a variety of microbial activities against the tested strains. Most compounds showed antimicrobial activity against S. aureus with an MIC range of 0.025 to 2.609 mM. The most active compound, 16c, exhibited superior activity against the S. aureus strain with an of MIC 0.025 mM among all tested compounds, outperforming both standard drugs ampicillin and sulfadiazine. The physicochemical–pharmacokinetic properties of the synthesized compounds were studied, and it was discovered that some compounds do not violate rule of five and have good bioavailability and drug-likeness scores. The five antimicrobial potent compounds with good physicochemical–pharmacokinetic properties were then examined for their inhibition of DHPS enzyme. According to the finding, three compounds, 16a–c, had IC50 values comparable to the standard drug and revealed that compound 16b was the most active compound with an IC50 value of 7.85 μg/mL, which is comparable to that of sulfadiazine (standard drug) with an IC50 value of 7.13 μg/mL. A docking study was performed to better understand the interaction of potent compounds with the binding sites of the DHPS enzyme, which revealed that compounds 16a–c are linked by two arene-H interactions with Lys220 within the PABA pocket. [ABSTRACT FROM AUTHOR]

In this study, a stepwise reaction afforded thiazolidinone-based benzothiazole derivatives 1–15, and the synthesized derivatives were then screened for biological significance and found to be the leading candidates against α-amylase and α-glucosidase enzymes. Almost all derivatives showed excellent to good activity ranging against α-amylase, IC50 = 2.10 ± 0.70 to 37.50 ± 0.70 μM, and α-glucosidase, IC50 = 3.20 ± 0.05 to 39.40 ± 0.80 μM. Some analogues such as 4 (2.40 ± 0.70 and 3.50 ± 0.70 μM), 5 (2.30 ± 0.05 and 4.80 ± 0.10 μM), and 6 (2.10 ± 0.70 and 3.20 ± 0.70 μM) were found with folds better activity than that of the standard drug acarbose (9.10 ± 0.10 and 10.70 ± 0.10 μM), respectively. Moreover, the structure–activity relationship (SAR) has been established for all compounds. A molecular docking study has been carried out to explore the binding interactions against α-amylase and α-glucosidase enzymes. [ABSTRACT FROM AUTHOR]

We report a comparative study of coordination behaviour of 2-(2-aminophenyl)benzothiazole (NH2-pbt) and its phosphorus-containing derivative, α-aminophosphine oxide (PCNH-pbt), towards zinc halides. The corresponding coordination compounds [Zn(L)2Hal2] (L = PCNH-pbt, Hal = Cl, 1 and Hal = Br, 2) and [Zn(L')Hal2] (L' = NH2-pbt, Hal = Cl, 3 and Hal = Br, 4) were obtained as single phases. As evidenced by single-crystal X-ray diffraction analysis, L' ligand coordinates to Zn in a chelate manner via two N atoms. Despite a similar coordination mode in complexes 3 and 4, the spatial geometry of the ligand differs notably, which implies a relatively high flexibility of NH2-pbt. The L ligand exhibits another coordination mode, binding with Zn only via the oxygen of the P=O group. The differences in the structures of NH2-pbt, 3 and 4, and their counterparts, PCNH-pbt, 1 and 2, induce differences in their solid-state photoluminescence properties. The former group of the compounds exhibits conventional single-band emission, while the latter group reveals two bands. The minor band at 450 nm is ascribed to a radiative transition for the regular amine species, while the major band at 520–550 nm can be associated either with the proton-transferred imine species (ESIPT mechanism) or with a charge transfer state (TICT) with a different geometry. [ABSTRACT FROM AUTHOR]

Riluzole is a benzothiazole derivative that has neuroprotective properties. In this work, to measure riluzole, a glassy carbon electrode was modified by graphene quantum dots and polymerization of a synthesized monomer (4-(1H-benzimidazole-2-yl)benzene-1,2-diol). Characteristics and morphology of the modified electrode were studied using scanning electron microscopy and Fourier transform infrared. Investigation of the electrochemical behaviour of riluzole on the electrode revealed the electrocatalytic effect of the modified electrode. The repeatability (RSD = 3.7%, n = 7), reproducibility (RSD = 4.2%, n = 4) and long-term stability (RSD = 5.3%, 30 days) of the modified electrode have been studied. The calibration curve was linear in the concentration range of 0.8 to 50 µmol l−1 riluzole and the limit of detection was found to be 0.1 µmol l−1 riluzole. The proposed method has been successfully applied to determine the riluzole in human blood serum samples. [ABSTRACT FROM AUTHOR]

Benzothiazoles (BTHs), commonly used in various industrial applications, have emerged as significant contaminants due to their widespread usage and potential adverse effects on ecosystems and human health. The aim of this study is to quantify and, for the first time, to characterize the particle size distribution of eight BTHs across twelve fractions of atmospheric aerosol representative of the urban boundary layer. Samples were collected from August to October 2023 in the urban area of Venice, located in the Po Valley, known for its poor air quality. Instrumental analysis was achieved via an UHPLC system coupled with a triple quadrupole mass spectrometer. All target compounds were present in the samples analyzed and most of them tended to distribute mainly in the fine fraction of aerosol (<1.8 μm). An exception is given by BTH-SO 3 H, which presents a bimodal distribution with maxima centered in the coarse fraction; this may imply a different source compared to other BTHs. BTH-SH is the most abundant benzothiazole derivative, suggesting tyre debris as the main source since it is the main compound used in vulcanizing accelerators in rubber manufacture. Given its mutagenic properties, its high relative abundance could be of concern for human health. of this work provide valuable insights into the distribution of BTHs in urban aerosols, laying the groundwork for future research aimed at better understanding their sources and environmental pathways, fate and impacts. [Display omitted] • Quantification via UHPLC-MS/MS of eight BTHs in size-segregated urban aerosol. • Characterization of BTHs' distribution across twelve particle size fractions. • Rooftop level aerosol composition as reflective of the urban background layer. • BTHs diagnostic ratios as possibile markers for photochemical processes. [ABSTRACT FROM AUTHOR]

[Display omitted] • Lower root uptake but higher upward translocation in plants were observed for 2-SH-BTH and 2-NH 2 -BTH. • Uptake and translocation of BTs by carrot is mainly driven by their lipophilicity. • BTs were rapidly metabolized in carrot and a total of 17 metabolites were identified. • The uptake and metabolism of BTs in carrot was structure-dependent. Tire additives, such as benzothiazole and its derivatives (collectively called BTs), are large-volume chemicals that are constantly emitted into agricultural environment via tire-road wearing and other actions. The potential accumulation of BTs in food crops depends largely on their metabolism in plants, which is poorly understood. Herein, we evaluated uptake and metabolism of six BTs in carrot callus and intact carrot plants to understand their structure-specific metabolism. All BTs were readily taken up by carrot roots, with their root concentration factors (RCF) ranging from 1.66 ± 0.01 to 2.95 ± 0.05. Although the tested BTs exhibited poor upward translocation from root to leaves (translocation factors < 1), the translocation factors of 2-methylbenzothiazole (0.79) and 2-aminobenzothiazole (0.65) were significantly higher than that of 2-methylbenzothiazole (0.18) and 2-(methylthio)benzothiazole (0.22). These results indicated the structure-dependent uptake and translocation of BTs in carrot. Correlation analysis between log K ow and log RCF or TF revealed that the hydrophobicity of BTs predominantly affected their root uptake and acropetal translocation in carrots. With the aid of high-resolution mass spectrometry, a total of 18 novel metabolites of BTs were tentatively identified, suggesting that BT compounds can be metabolized by carrot callus. The proposed metabolites of BTs include four hydroxylated products, one demethylated product, five glycosylated products and eight amino acid conjugated products, revealing that glycosylation and amino acid conjugation were the dominant transformation pathways for BT metabolism in carrot. However, the detected species of metabolites for six BTs varied distinctly, indicating structure-specific metabolism of BTs in plants. The findings of this study improve our understanding of structure-dependent fate and transformation of BTs in plants. Since BTs metabolites in food crops could present an unintended exposure route to consumers, the structure-specific differences of BTs uptake, metabolism and accumulation in plants must be considered when addressing human dietary exposure risks. [ABSTRACT FROM AUTHOR]

The present study reports the new thiazole (A-L) derivatives based on benzothiazole fused triazole which were synthesized and assessed against thymidine phosphorylase and α-glucosidase enzymes. Several compounds with the same basic structure but different substituents were found to have high activity against the targeted enzymes, while others with the same basic skeleton but different substituents were found to have medium to low activity among the members of tested series. These analogs showed a varied range of inhibition in both case thymidine phosphorylase and alpha glucosidase, A (IC 50 = 7.20 ± 0.30 µ M and IC 50 = 1.30 ± 0.70 µ M), B (IC 50 = 8.80 ± 0.10 µ M and IC 50 = 2.10 ± 0.30 µ M), C (IC 50 = 8.90 ± 0.40 µ M and IC 50 = 3.20 ± 0.20 µ M) and thiazole containing analogs such as G (IC 50 = 11.10 ± 0.20 µ M and IC 50 = 7.80 ± 0.20 µ M) and H (IC 50 = 12.30 ± 0.30 µ M and IC 50 = 6.30 ± 0.20 µ M). When compared with standard drugs 7-Deazaxanthine, 7DX (IC 50 = 10.60 ± 0.50 µM) and acarbose (IC 50 = 4.30 ± 0.30 µM) respectively. These analogs were also subjected to molecular docking studies which indicated the binding interaction of molecules with active sites of the enzyme and strengthen the drug profile of these compounds. ADMET studies also predict the drug-like properties of these compounds, with no violations of drug likeness rules. [Display omitted] • We have synthesized novel benzothiazole-triazole based thiazole derivatives. • Isolated compounds were evaluated for in vitro against thymidine phosphorylase and α-glucosidase. • A number of the compounds exhibited excellent activity, some better than the reference standards. • Molecular docking and ADMET study determined binding interactions of potent compounds and their toxicity respectively. • Exploration of better potentials via a series of studies was presented. [ABSTRACT FROM AUTHOR]

• Benzofuran derivatives were shown to induce IFN-I expression in a STING-dependent luciferase assay. • Activity as STING agonist was confirmed by mutagenesis studies. • Antiviral effect of BZFs was demonstrated on HCoV-229E and SARS-CoV-2 replication. • IFN-I mediated antiviral effect was confirmed by immunofluorescent analysis. The Stimulator of Interferon Genes (STING) is involved in cytosolic DNA sensing and type I Interferons (IFN-I) induction. Aiming to identify new STING agonists with antiviral activity and given the known biological activity of benzothiazole and benzimidazole derivatives, a series of benzofuran derivatives were tested for their ability to act as STING agonists, induce IFN-I and inhibit viral replication. Compounds were firstly evaluated in a gene reporter assay measuring luciferase activity driven by the human IFN-β promoter in cells expressing exogenous STING (HEK293T). Seven of them were able to induce IFN-β transcription while no induction of the IFN promoter was observed in the presence of a mutated and inactive STING, showing specific protein-ligand interaction. Docking studies were performed to predict their putative binding mode. The best hit compounds were then tested on human coronavirus 229E replication in BEAS-2B and MRC-5 cells and three derivatives showed EC 50 values in the μM range. Such compounds were also tested on SARS-CoV-2 replication in BEAS-2B cells and in Calu-3 showing they can inhibit SARS-CoV-2 replication at nanomolar concentrations. To further confirm their IFN-dependent antiviral activity, compounds were tested to verify their effect on phospho-IRF3 nuclear localization, that was found to be induced by benzofuran derivatives, and SARS-CoV-2 replication in Vero E6 cells, lacking IFN production, founding them to be inactive. In conclusion, we identified benzofurans as STING-dependent immunostimulatory compounds and host-targeting inhibitors of coronaviruses representing a novel chemical scaffold for the development of broad-spectrum antivirals. [ABSTRACT FROM AUTHOR]

The antiproliferative effects played by benzothiazoles in different cancers have aroused the interest for these molecules as promising antitumor agents. In this work, a library of phenylacetamide derivatives containing the benzothiazole nucleus was synthesized and compounds were tested for their antiproliferative activity in paraganglioma and pancreatic cancer cell lines. The novel synthesized compounds induced a marked viability reduction at low micromolar concentrations both in paraganglioma and pancreatic cancer cells. Derivative 4l showed a greater antiproliferative effect and higher selectivity index against cancer cells, as compared to other compounds. Notably, combinations of derivative 4l with gemcitabine at low concentrations induced enhanced and synergistic effects on pancreatic cancer cell viability, thus supporting the relevance of compound 4l in the perspective of clinical translation. A target prediction analysis was also carried out on 4l by using multiple computational tools, identifying cannabinoid receptors and sentrin-specific proteases as putative targets contributing to the observed antiproliferative activity. [ABSTRACT FROM AUTHOR]

Despite extensive studies and the great variety of existing anticancer agents, cancer treatment remains an aggravating and challenging problem. Therefore, the development of novel anticancer drugs with a better therapeutic profile and fewer side effects to combat this persistent disease is still necessary. In this study, we report a novel series of benzothiazole and chromone derivatives that were synthesized and evaluated for their anticancer activity as an inhibitor of ATR kinase, a master regulator of the DDR pathway. The cell viability of a set of 25 compounds was performed using MTT assay in HCT116 and HeLa cell lines, involving 72 h incubation of the compounds at a final concentration of 10 µM. Cells incubated with compounds 2c, 7h and 7l were found to show viability ≤50%, and were taken forward for dose–response studies. Among the tested compounds, three of them (2c, 7h and 7l) showed higher potency, with compound 7l exhibiting the best IC50 values in both the cell lines. Compounds 2c and 7l were found to be equally cytotoxic towards both the cell lines, namely, HCT116 and HeLa, while compound 7h showed better cytotoxicity towards HeLa cell line. For these three compounds, an immunoblot assay was carried out in order to analyze the inhibition of phosphorylation of Chk1 at Ser 317 in HeLa and HCT116 cells. Compound 7h showed inhibition of pChk1 at Ser 317 in HeLa cells at a concentration of 3.995 µM. Further analysis for Chk1 and pChk1 expression was carried out in Hela cells by treatment against all the three compounds at a range of concentrations of 2, 5 and 10 µM, wherein compound 7h showed Chk1 inhibition at 2 and 5 µM, while pChk1 expression was observed for compound 7l at a concentration of 5 µM. To support the results, the binding interactions of the compounds with the ATR kinase domain was studied through molecular docking, wherein compounds 2c, 7h and 7l showed binding interactions similar to those of Torin2, a known mTOR/ATR inhibitor. Further studies on this set of molecules is in progress for their specificity towards the ATR pathway. [ABSTRACT FROM AUTHOR]

Twelve new compounds including 2-aminobenzamide derivatives bearing benzothiazole and phenylamine moiety were designed and synthesized. The synthesized compounds were tested their cytotoxic activity against A549 and SW480 tumor cell lines. Compounds 3a and 3c exhibited cytotoxicity toward A549 cell line with IC50 values of 24.59 and 29.59 µM, respectively. [ABSTRACT FROM AUTHOR]

Sixteen compounds bearing a benzothiazole moiety were synthesized as potential tyrosinase inhibitors and evaluated for mushroom tyrosinase inhibitory activity. The compound 4-(5-(trifluoromethyl)benzo[d]thiazol-2-yl)benzene-1,3-diol (compound 1b) exhibited the highest tyrosinase activity inhibition, with an IC50 value of 0.2 ± 0.01 μM (a potency 55-fold greater than kojic acid). In silico results using mushroom tyrosinase and human tyrosinase showed that the 2,4-hydroxyl substituents on the phenyl ring of 1b played an important role in the inhibition of both tyrosinases. Kinetic studies on mushroom tyrosinase indicated that 1b is a competitive inhibitor of monophenolase and diphenolase, and this was supported by docking results. In B16F10 murine melanoma cells, 1a and 1b dose-dependently and significantly inhibited melanin production intracellularly, and melanin release into medium more strongly than kojic acid, and these effects were attributed to the inhibition of cellular tyrosinase. Furthermore, the inhibition of melanin production by 1b was found to be partially due to the inhibition of tyrosinase glycosylation and the suppression of melanogenesis-associated genes. Compound 1c, which has a catechol group, exhibited potent antioxidant activities against ROS, DPPH, and ABTS, and 1b also had strong ROS and ABTS radical scavenging activities. These results suggest that 5-(trifluoromethyl)benzothiazole derivatives are promising anti-tyrosinase lead compounds with potent antioxidant effects. [ABSTRACT FROM AUTHOR]

Benzothiazole analogs are very interesting due to their potential activity against several infections. In this research, five benzothiazole derivatives were studied using density functional theory calculations. The optimized geometry, geometrical parameters and vibrational spectra were analyzed. The charge distribution diagrams, such as FMO (HOMO-LUMO), energies of HOMO-LUMO, polarizability, hyperpolarizability, MESP and density of states, were calculated. The computed energies of HOMO and LUMO showed that the transfer of charge occurred within the compound. The effect of the change of substituents on the ring on the value of the HOMO-LUMO energy gap was also observed. It was observed that, in this series, compound 4 with CF3 substituent had the lowest energy gap of HOMO-LUMO, and compound 5 with no substituent had highest HOMO-LUMO energy gap. From the energies of HOMO and LUMO, the reactivity descriptors, such as electron affinity (A), ionization potential (I), chemical softness (σ), chemical hardness (ƞ), electronic chemical potential (μ), electrophilicity index (ω), were calculated. In addition, the 13C and 1H NMR chemical shifts of the molecules were calculated using the gauge-independent atomic orbit (GIAO) method; the shifts were in good agreement with the experimental values. The anti-bacterial potential of compounds 1 to 5 was tested by molecular docking studies toward target proteins 2KAU and 7EL1 from Klebsiella aerogenes and Staphylococcus aureus. Compounds 3 and 1 showed high affinity toward 2KAU and 7EL1, respectively. [ABSTRACT FROM AUTHOR]

Background: The magnetic nano-catalysts improve the contact between substrates and catalyst considerably and simple isolation of catalyst from reaction mixture. In this study, Fe3O4@nano-almondshell@OSi(CH2)3/2-(1-piperazinyl)ethylamine/Cu(II) abbreviated (FNAOSiPPEA/Cu(II)), was prepared, characterized and applied for the synthesis of 4H-pyrimido[2,1-b]benzothiazole. Results: FNAOSiPPEA/Cu(II) as a bio-based nano-catalyst was prepared from the complexation of copper on 2-(1-piperazinyl)ethylamine, which was immobilized on Fe3O4@nano-almondshell@OSi(CH2)3 section. This new heterogeneous bifunctional Lewis acid/Bronsted base catalyst (FNAOSiPPEA/Cu(II)) was characterized by various techniques such as FT-IR, FESEM, TGA, EDS-MAP, XRD, VSM, BET, TEM, and XPS. So, the catalytic performance of this recyclable nano-catalyst was determined to promote the synthesis of 4H-pyrimido[2,1-b]benzothiazole derivatives at 100 °C under solvent-free conditions. Conclusions: Magnetite nano-catalyst of (FNAOSiPPEA/Cu(II)) is easily separated by an external magnet and successfully reused up at least 3 times with a slight loss of yield of the desired product. [ABSTRACT FROM AUTHOR]

Numerous benzothiazole derivatives are used in organic synthesis, in various industrial and consumer products, and in drugs, with a wide spectrum of biological activity. As the properties of the benzothiazole moiety are strongly affected by the nature and position of substitutions, in this review, covering the literature from 2016, we focus on C-2-substituted benzothiazoles, including the methods of their synthesis, structural modification, reaction mechanisms, and possible pharmacological activity. The synthetic approaches to these heterocycles include both traditional multistep reactions and one-pot atom economy processes using green chemistry principles and easily available reagents. Special attention is paid to the methods of the thiazole ring closure and chemical modification by the introduction of pharmacophore groups. [ABSTRACT FROM AUTHOR]

In elderly aged people, Parkinson’s disease is reported as 2nd most prevailing neuro-degenerative disease. Presently benzothiazole derivatives are gaining attention after showing positive results in various animal models for the investigation of different motor-diseases. In Current work, the 2- (2 Thienyl)Benzothiazoline is synthesized and its therapeutic effect was evaluated against rotenone-induced Parkinson’s disease. It was expected to obtain the positive results in the treatment because thiophen group has been successfully reported in various literature as effective agent in the treatment of cognitive and locomotory disease. So, we used a Parkinson’s inducive compound rotenone and injectedit intraperitoneally. The dose that we were used was 1.5mg/kg and treatment proceeded for 8 days in rats as rotenone inhibit the functioning of mitochondrial complex I. Administration of 2- (2 Thienyl)Benzothiazoline (10mg/kg per day) was already started 15 days prior to rotenone dose injection. The effects of both pre-treatment and without pre-treatment of 2- (2 Thienyl)Benzothiazoline were assessed by the use of various motor parameters of behavior such as pole test and Kondziela’s inverted screen test for checking muscular strength, whereas inclined plane test, open field test and Rota rod test for motor coordination. Pre-treatment with drug reversed the gross motor impairments which were produced by rotenone. We conclude that 2- (2 Thienyl)Benzothiazoline, like its other candidate drug also protects against destructive effects of the compound rotenone and itcan be used as beneficial drug against various neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

A series of novel tetrazine derivatives, containing benzothiazole framework, were prepared during the coupling reactions of some diazotized 2-aminobenzo[d]thiazole derivatives with p-acetaminophen. Their structures were elucidated based on NMR and MS spectrometry. The anticancer activity and the safety of the synthesized compounds along with the entire precursors were assessed against three human cancer cell lines and a normal cell line. All the synthesized compounds showed selective cytotoxic activity against the cancer cell lines used in comparison to the normal Vero cell line. Their IC50 values varied from 2.02 to 171.67 µM. [ABSTRACT FROM AUTHOR]

The main objective of this research was to design non-fullerene acceptors (NFAs) A--D--A framework, using carbazole and benzothiazole derivatives. Density functional theory (DFT) was used to calculate the geometry optimized structures and electronic properties at B3LYP functional with a 6-311G basis set in the gas and solvent phase. The frontier molecular orbitals (FMO), bandgap, open-circuit voltage (VOC) and dipole moments of these developed acceptors have been calculated. The theoretical UV absorption spectra were calculated from time-dependent DFT with the same level of theory used DFT method. They show a suitable bandgap (2.24-2.93 eV) and dipole moment (1.8-10.8 Debye). The maximumwavelength (λmax) for all studied molecules in the range is 665.17-679.97 in both gas and solvent. A slight redshift was observed in all acceptors selected for chlorobenzene compared with gas phase absorption. The NFA A11 has the lowest bandgap energy (2.24 eV), gas-phase excitation energy (1.86 eV) and chlorobenzene excitation energy (1.86 eV). As a result, A11 is predicted to be a good contender for organic NFAs in the future. The open-circuit voltage (VOC) values range from 1.53 to 2.56 eV. Consequently, the optoelectronic, molecular orbital distribution and A11 and A12 molecules were suitable acceptors for NFAs. [ABSTRACT FROM AUTHOR]