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Background: Benzothiazoles are reported to have bioorganic and pharmaceutical chemistry applications., Introduction: A series of substituted N-bromoamido-2-aminobenzothiazoles was synthesized from substituted anilines via 2-aminobenzothiazoles and it was further evaluated for its antimicrobial activity., Methods: All the newly synthesized compounds were characterized by FT-IR, NMR and mass spectra and purity profiles were studied by HPLC analysis. The antimicrobial testing (MIC determination) was newly performed with agar micro-broth dilution method for these analogs., Results: Among the synthesized compound 3b showed the highest activity with MIC value of 3.12 μg/mL against Bacillus, E. coli, S. aureus and Klebsiella and 6.25 μg/mL against C. albicans. The ADME properties as calculated by using Qikprop were found within acceptable range. Derivatives shows a good-moderate binding affinity towards target Cytochrome P450 14 alpha-sterol demethylase (CYP51) (PDB ID: 1EA1)., Conclusion: Our in-silico and in-vitro studies on a series of substituted aminobenzothiazoles may be helpful for further designing of more potent antimicrobials in future., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Infectious diseases are a major threat in the developing world and the discovery of novel antimicrobial agents remains to be crucial due to acquired resistance by the microorganisms. Additionally, various diseases can be prevented with antioxidant agents as they can eliminate the harmful effects of reactive oxygen species., Objective: In this study, it was aimed to synthesize novel compounds bearing N-(6- methoxybenzothiazol-2-yl)-3-(4-substitued piperazinyl)propanamide backbone that had antimicrobial and antioxidant activities. Mechanisms of activity were aimed to be revealed by docking studies., Methods: Antimicrobial activities were tested by agar-based disc diffusion assay, and antioxidant activities were determined by CUPRAC assay., Results: In agar-based disc diffusion assay, the most active compounds were 2b and 2e against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and Candida albicans. Compounds 2e and 2j showed promising antioxidant activity in CUPRAC assay. Docking studies were performed to optimize the interactions of compounds with DNA gyrase subunit B of S. aureus. Under the light of docking studies, a new compound with potential GyrB inhibition was designed. Antioxidant activity was also supported by docking studies on superoxide dismutase 1 enzyme in which interactions with key residues were observed., Conclusion: Ten novel benzothiazole-piperazine derivatives were synthesized and their antimicrobial and antioxidant activities were evaluated. Superoxide dismutase 1 enzyme was suggested to be a possible target for the antioxidant activity of the series., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Based on benzoxazole and benzothiazole scaffold as an important pharmacophore, two series of 2-(aryloxymethyl) benzoxazole and benzothiazole derivatives were synthesized and their antifungal effects against eight phytopathogenic fungi were evaluated. Compounds 5a , 5b , 5h , and 5i exhibited significant antifungal activities against most of the pathogens tested. Especially 5a , 5b , 5h , 5i , 5j , and 6h inhibited the growth of F. solani with IC 50 of 4.34⁻17.61 μg/mL, which were stronger than that of the positive control, hymexazol (IC 50 of 38.92 μg/mL). 5h was the most potent inhibitor (IC 50 of 4.34 μg/mL) against F. Solani , which was about nine times more potent than hymexazol. Most of the test compounds displayed significant antifungal effects against B. cinerea (IC 50 of 19.92⁻77.41 μg/mL), among them, 5a was the best one (IC 50 of 19.92 μg/mL). The structure-activity relationships (SARs) were compared and analyzed. The result indicates that the electron-drawing ability and position of the substituents have a significant impact on biological activities. Furthermore, docking studies were carried out on the lipid transfer protein sec14p from S. cerevisiae , and preliminarily verified the antifungal activities. Taken together, these results provide 2-(phenoxymethyl)benzo[d]oxazole as an encouraging framework that could lead to the development of potent novel antifungal agents.

A series of new azoalkyl ether imidazo[2,1-b]benzothiazoles were developed via a convenient synthetic procedure. The antimicrobial assays showed that a good number of the prepared derivatives exhibited significant inhibitory properties against most of the tested strains. Especially 2-methyl-5-nitroimidazole derivative 5a presented superior inhibit activity against MRSA and B. typhi with MIC = 4 μg/mL and MIC = 1 μg/mL, respectively. The highly active compound 5a showed low toxicity against mammalian cells without obvious triggering of the development of bacterial resistance, and it also possessed rapid bactericidal efficacy. Molecular docking study exposed that the active molecule 5a could interact with the active site of S. aureus gyrase through hydrogen bond. Quantum chemical studies were also performed to explain the high antibacterial activity. Further investigation revealed that compound 5a could significantly associate with gyrase-DNA complex by mean of hydrogen bonds and could efficiently intercalate into MRSA DNA to form 5a-DNA supramolecular complex, which impart potent bioactivity., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Highly diastereoselective synthesis of some novel benzothiazole-substituted β-lactam hybrids was achieved starting from (benzo[d]thiazol-2-yl)phenol as an available precursor. This is the first time (benzo[d]thiazol-2-yl)phenoxyacetic acid has been used as ketene source in synthesizing monocyclic 2-azetidinones. These compounds were evaluated for their antimicrobial activities against a large panel of Gram-positive and Gram-negative bacterial strains and moderate activities were encountered. Antimalarial data revealed that adding methoxyphenyl or ethoxyphenyl group on the β-lactam ring makes compounds that are more potent. Moreover, hemolytic activity and mammalian cell toxicity survey of the compounds showed their potential as a medicine., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Benzothiazole analogues are of interest due to their potential activity against malarial and microbial infections. In search of suitable antimicrobial and antimalarial agents, we report here the synthesis, characterization and biological activities of benzothiazole analogues (J 1-J 10). The molecules were characterized by IR, Mass, 1 H NMR, 13 C NMR and elemental analysis. The in vitro antimicrobial activity was investigated against pathogenic strains; the results were explained with the help of DFT and PM6 molecular orbital calculations. In vitro cytotoxicity and genotoxicity of the molecules were studied against S. pombe cells. In vitro antimalarial activity was studied. The active compounds J 1, J 2, J 3, J 5 and J 6 were further evaluated for enzyme inhibition efficacy against the receptor Pf-DHFR, computational and in vitro studies were carried out to examine their candidatures as lead dihydrofolate reductase inhibitors., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

A series of compounds with benzothiazole and amide-imidazole scaffolds were designed and synthesized to combat the increasing incidence of drug-resistant fungal infections. The antifungal activity of these compounds was evaluated in vitro, and their structure-activity relationships (SARs) were evaluated. The synthesized compounds showed excellent inhibitory activity against Candida albicans and Cryptococcus neoformans. The most potent compounds 14o, 14p, and 14r exhibited potent activity, with minimum inhibitory concentration (MIC) values in the range of 0.125-2 μg/mL. Preliminary mechanism studies revealed that the compound 14p might act by inhibiting the CYP51 of Candida albicans. The SARs and binding mode established in this study are useful for further lead optimization., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

A series of 2-aminobenzothiazole and benzimidazole analogs based on the clathrodin scaffold was synthesized and investigated for their antimicrobial and antiproliferative activities as well as for their effects in hepatitis C virus (HCV) replicon model. Compound 7, derived from 2-aminobenzothiazole, exhibited moderate antimicrobial activity only against the Gram-positive bacterium, Enterococcus faecalis. In the antiviral assay, compounds 4d and 7 were found to suppress the HCV replicon by >70%, but also to exhibit cytotoxicity against the host cells (35 and 44%, respectively). Compounds 4a and 7 demonstrated good activity in the antiproliferative assays on the human melanoma cell line A-375. To assess the selectivity of the effects between cancerous and noncancerous cells, a mouse fibroblast cell line was used. The IC50 values for compound 7 against the melanoma cell line A-375 and the fibroblast cell line BALB/c 3T3 were 16 and 71 µM, respectively, yielding fourfold selectivity toward the cancer cell line. These results suggest that compound 7 should be studied further in order to fully explore its potential for drug development., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

An organic charge transfer complex, 2-aminobenzothiazolium-4-methylbenzenesulphonate (ABPTS) was synthesized and single crystals grown by slow solvent evaporation solution growth technique at ambient temperature. The single crystal X-ray diffraction analysis was carried out to establish the molecular structure of the title crystal. FT-IR spectral study was carried out to identify the various functional groups present in the crystal. The (1)H and (13)C spectra were recorded to further confirm the molecular structure of the CT complex. The TG/DTA analyses were carried out to establish the thermal stability of the complex. The antibacterial and antifungal activities of synthesized complex were examined against various bacteria and fungi strains, to identify the antibacterial and antifungal activity. The DNA binding profile of the complex has been investigated through absorption spectroscopy and complex has intrinsic binding constant 3.6 × 10(4) M(-1). A gel electrophoresis assay demonstrated the ability of the complex to cleave the pBR322 DNA. The free radical scavenging activity of the complex has been determined against DPPH, OH and ABTS radicals., (Copyright © 2015. Published by Elsevier B.V.)

A new series of N,O-acetals were prepared via a simple one-pot reaction by the condensation of 2-amino-methybenzothiazole with aldehydes and alcohols. The title compounds were obtained in moderate to good yields in the presence of acid catalyst. Bioassay results indicated that some synthesized compounds had good herbicidal activity against both dicotyledon and monocotyledon weeds. This investigation provided a new type of herbicidal lead compounds, as well as its facile preparation method., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Antimicrobial screening of several novel 4-thiazolidinones with benzothiazole moiety has been performed. These compounds were evaluated for antimicrobial activity against a panel of bacterial and fungal strains. The strains were treated with these benzothiazole derivatives at varying concentrations, and MIC's were calculated. Structures of these compounds have been determined by spectroscopic studies viz., FT-IR, 1H NMR, 13C NMR and elemental analysis. Significant antimicrobial activity was observed for some members of the series, and compounds viz. 3-(4-(benzo[d]thiazol-2-yl) phenyl-2-(4-methoxyphenyl)thiazolidin-4-one and 3-(4-(benzo[d]thiazol-2-yl)phenyl)-2-(4-hydroxy phenyl)thiazolidin-4-one were found to be the most active against E.coli and C. albicans with MIC values in the range of 15.6-125 microg/ml. Preliminary study of the structure-activity relationship revealed that electron donating groups associated with thiazolidine bearing benzothiazole rings had a great effect on the antimicrobial activity of these compounds and contributes positively for the action. DNA cleavage experiments gave valuable hints with supporting evidence for describing the mechanism of action and hence showed a good correlation between their calculated MIC's and its lethality.

A variety of pyrimidinyl benzoxazoles, benzothiazoles and benzimidazoles linked by thio, methylthio and amino moieties were prepared and studied their antimicrobial and cytotoxic activities. The compound pyrimidinyl bis methylthio benzimidazole 22 was a potent antimicrobial agent particularly against Staphylococcus aureus (29 mm, MIC 12.5 μg/mL) and Penicillium chrysogenum (38 mm, MIC 12.5 μg/mL). The amino linked pyrimidinyl bis benzothiazole 24 exhibited cytotoxic activity on A549 cells with IC50 value of 10.5 μM., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

The synthesis of a variety of N-alkylated 2,3,3-trimethylindolenines and 2-methylbenzothiazoles is reported herein. Their potential as antifungal agents is evaluated by preliminary screening against Saccharomyces cerevisiae (S. cerevisiae), Schizosaccharomyces pombe (S. pombe), and Candida albicans (C. albicans). Statistical analyses illustrate a strong relationship between chain length and growth inhibition for S. cerevisiae and S. pombe (p < 0.0001 in every case). Of particular interest is the activity of both sets of compounds against S. cerevisiae, as this is emerging as an opportunistic pathogen, especially in immunosuppressed and immunocompromised patients. Bioassays were set up to compare the efficacy of our range of N-alkylated compounds against classic antifungal agents; Amphotericin B and Thiabendazole., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

A new series of 6-substituted 2-aminobenzothiazole derivatives were synthesized and screened in vitro as potential antimicrobials. Almost all the compounds showed antifungal activity. In particular, compounds 1n,o, designed on the basis of molecular modeling studies, were the best of the series, showing MIC values of 4-8 μg/mL against Candida albicans, Candida parapsilosis and Candida tropicalis. None of the two compounds did show any cytotoxicity effect on human THP-1 cells., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

In an attempt to design and synthesize a new class of antimicrobials, dialkyne substituted 2-aminobenzothiazole was reacted with various substituted aryl azides to generate a small library of 20 compounds (3a-t) by click chemistry. Structures of the newly synthesized compounds were established on the basis of spectral data. These compounds were screened for their antibacterial activity against Gram+ bacteria (Staphylococcus aureus and Enterococcus faecalis), Gram- bacteria (Salmonella typhi, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Shigella boydii) and antifungal activity against Candida tropicalis, Candida albicans, Candida krusei, Cryptococcus neoformans) as well as molds (Aspergillus niger, Aspergillus fumigatus). The compound 3e showed maximum potency against all Gram+/gram- bacterial strains with MIC value 3.12 μg/ml, which is two fold more active as compared to standard drug ciprofloxacin (MIC 6.25 μg/ml). However, all compounds were found ineffective against S. boydii (clinical isolate). Further, only one compound 3n was found to be the most active against all fungal strains with MIC value in the range of 1.56 μg/ml-12.5 μg/ml while the remaining compounds showed moderate to weak antifungal activity., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

A series of s-triazolobenzothiazolylthioacetyl/propionyl amino acid derivatives were synthesized with the aim of evaluating their antifungal activity. Their chemical structures were confirmed by (1)H, (13)C NMR, IR, mass spectrometry and elemental analyses. The synthesized derivatives were screened for their antifungal activity against Aspergillus flavus and Candida albicans. Five compounds (3, 5, 7c, 8 and 17) were found to possess high activity comparable to fluconazole at 100 μg/mL against C. albicans., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

A series of new N-[(benzo)thiazol-2-yl]-2/3-[3,4-dihydroisoquinolin-2(1H)-yl]ethan/propanamide derivatives was synthesized and characterized by (1)H, (13)C NMR and IR spectroscopy and mass-spectrometry. A single crystal X-ray study of N-(1,3-benzothiazol-2-yl)-2-[3,4-dihydroisoquinolin-2(1H)-yl]ethanamide is reported to determine its conformational feature. The investigated compounds were found to be active in psychotropic in vivo, anti-inflammatory in vivo and cytotoxicity in vitro screening. They possess marked sedative action, reveal high anti-inflammatory activity, have selective cytotoxic effects and NO-induction ability concerning tumour cell lines. Some of the compounds synthesized demonstrate antimicrobial action. An attempt was made to correlate the biological results with their structural characteristics and physicochemical parameters. Some specific combinations of types of activities for the synthesized compounds have been revealed., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

In this study, a series of N-substituted 2-aminobenzothiazoles was prepared according to a recently developed method. Twelve compounds were tested for their activity related to the inhibition of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. Primary in vitro screening of the discussed compounds was also performed against fungal, bacterial and mycobacterial species. The biological activities of some compounds were comparable or higher than the standards phenoxymethylpenicillin or pyrazinamide. The most effective compounds demonstrated insignificant toxicity against the human monocytic leukemia THP-1 cell line. For all compounds, the structure-activity relationships are discussed., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

A series of new 3-[(5-aryl-1,3,4-oxadiazol-2-yl)methy])benzo[d]thiazol-2(3H)-ones were synthesized by reaction of (5-substituted-2-oxobenzothiazolin-3-yl)-acetohydrazide with various aromatic acids in POCl(3) under reflux conditions. The structures of the title compounds were confirmed by ¹H-NMR, ¹³C-NMR, IR, MS and elemental analysis. Furthermore, the structure of compound 4i was determined by single-crystal X-ray diffraction. The preliminary bioassy results indicated that some of them showed moderate inhibition activity against Colletotrichum orbiculare, Botrytis cinerea and Rhizoctonia solani.

In this study, a series of novel 1,2,4-triazolo-[3,4-b]-1,3,4-thiadiazole (6a-g) and 1,3,4-oxadiazole (7a-g, 8) were synthesized from N-(6-chlorobenzo[d]thiazol-2-yl) hydrazine carboxamide derivatives of benzothiazole class. Antimicrobial properties of the title compound derivatives were investigated against one Gram (+) bacteria (Staphylococcus aureus), three Gram (-) bacteria (Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae) and five fungi (Candida albicans, Aspergillus niger, Aspergillus flavus, Monascus purpureus and Penicillium citrinum) using serial plate dilution method. The investigation of antibacterial and antifungal screening data revealed that all the tested compounds showed moderate to good inhibition at 12.5-100 µg/mL in DMSO. It has been observed that triazolo-thiadiazole derivatives are found to be more active than 1,3,4-oxadiazole derivatives against all pathogenic bacterial and fungal strains.

New antimicrobial agents, imidazo[1,2-a]pyridine and imidazo[2,1-b][1,3]benzothiazole, have been synthesized. Their antimicrobial activities were conducted against various Gram-positive, Gram-negative bacteria and fungi. Compounds 6c, 7a, 10b, 11a, 12b, 14a, 14b, 15a and 15b, exerted strong inhibition of the investigated bacterial and fungal strains compared to control antibiotics amoxicillin and cefixime and the antifungal agent fluconazole. Results from this study showed that the nature of the substituents on the armed aryl groups determines the extent of the activity of the fused imidazopyridine and/or imidazobenzothiazole derivatives. Preliminary structure-activity observations revealed that bromo-fluoro substituents enhanced the antimicrobial activity significantly compared to other substituents., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

A series of 2-phenylbenzothiazoles has been synthesized either by i) condensation of different aromatic aldehydes with 2-aminothiophenol or ii) condensation of N-(2-chlorophenyl)benzothioamides in KOH catalyzed by potassium fericyanide. The structures of synthesized compounds were confirmed by IR, MS, and (1)H-NMR. The results of biological activity screening showed that six compounds including 2-phenylbenzothiazol (1a), 2-(2-chlorophenyl)benzothiazole (1b), 2-(3-chlorophenyl)benzothiazole (1c), 2-(4-hydroxyphenyl)benzothiazole (1e), 2-(4-dimethylaminophenyl)benzothiazole (1h) and 2-(2,3,4-trimethoxyphenyl)benzothiazole (1i) exhibited significant antibacterial activities; two compounds (1a, 1e) exhibited antifungal activities. Especially, 1e showed considerable antimicrobial activity against both A. niger and F. oxysporum. The brominated derivative of 1e displayed extended spectrum against all four bacterial strains tested with lower MIC values. In vitro cytotoxicity of the synthesized compounds was evaluated on three cancer cell lines (A549, HT1080, MCF7-MDR). The results indicated that three compounds (1e, 1g, 1i) exhibited significant cytotoxic activity on A549 and MCF7-ADR cells (IC(50), 10.07-13.21 μg/ml). Brominated and nitrated derivatives (1k, 1l, respectively) of 1e exhibited even more potent cytotoxicity.

In this study, we report the antimycobacterial and antimicrobial evaluation of newly synthesized 3-(3-pyridyl)-5-(4-methoxyphenyl)-4-(N-substituted-1,3-benzothiazol-2-amino)-4H-1,2,4-triazole 6a-j in good yields. All the synthesized compounds have been established by elemental analysis, IR, ¹H NMR, ¹³C-NMR and Mass spectral data. In-vitro antimycobacterial activity was carried out against (Mycobacterium tuberculosis) H₃₇Rv strain using Lowenstein-Jensen medium and antimicrobial activity against two Gram positive bacteria (Staphylococcus aureus, Streptococcus pyogenes), two Gram negative bacteria (Escherichia coli, Pseudomonas aeruginosa) and three fungal species (Candida albicans, Aspergillus niger, Aspergillus clavatus) using the broth microdilution method. Compounds 2e, 6a, 6g, 6h, and 6j exhibited promising antimicrobial activity whereas compound 6j showed very good antimycobacterial activity.

Enaminonitrile 2 was used as key intermediate for the synthesis of polyfunctionally substituted heterocycles (e.g. pyrazoles, isoxazole, pyrimidines, thiazolo[3,2-a]pyrimidine, tetrazolo[1,5-a]pyrimidine, pyrido[1,2-a]pyrimidine, 1,5-benzodiazepine, and pyrazolo[1,5-a]pyrimidine) incorporating benzothiazole moiety via its reactions with some N-nucleophiles. The newly synthesized compounds were characterized by IR, (1)H NMR and mass spectral studies. Representative compounds of the synthesized products were tested and evaluated as antimicrobial agents.

Polyfluorinated 2-benzylthiobenzothiazoles 3a-l are prepared via a microwave-assisted, one-pot procedure. The advantages, such as good to excellent yields, shorter reaction time (14-21min), readily available starting material, and simple purification procedure, distinguish the present protocol from other existing methods used for the synthesis of 2-benzylthiobenzothiazoles. Bioassay indicated that most of the compounds showed significant fungicidal activity against Rhizoctonia solani, Botrytis cinereapers, and Dothiorella gregaria at a dosage of 50microg/mL. Interestingly, compared to the control of commercial fungicide, triadimefon, compound 3c exhibited much higher activities against R. solani, B. cinereapers, and D. gregaria, which showed that the polyfluorinated 2-benzylthiobenzothiazoles can be used as lead compound for developing novel fungicides.

A series of 2-{[2'-(3''-chloro-2''-oxo-4''-substitutedaryl-1''-azetidinyl)-1',3'-thiazol-4'-yl] thio}benzothiazoles (4a-4e) and 2-{[(2'-(2''-substitutedaryl-4''-thiazolidinon-3''-yl)-1',3'-thiazol-4'-yl]thio}benzothiazoles (5a-5e) have been synthesized from 2-[(2'-substitutedarylidenylimino-1',3'-thiazol-4'-yl)thio]benzothiazoles (3a-3e). The structure of these compounds has been elucidated by elemental (C, H, N) and spectral (IR, (1)H-NMR, Mass) analysis. Furthermore, compounds 3a-3e, 4a-4e, and 5a-5e were screened for insecticidal activity against Periplaneta americana and antifungal, antibacterial activities in vitro against different strains of fungi and bacteria. Out of the fifteen compounds tested, compound 5b, 2-{[2'-(2''-p-hydroxy-m-methoxyphenyl)-4''-thiazolidinon-3''-yl)-1',3'-thiazol-4'-yl]thio}benzothiazole, was found to possess most prominent insecticidal activity.