Synthesis, SAR, Molecular Docking and Anti-Microbial Study of Substituted N-bromoamido-2-aminobenzothiazoles.

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.

Synthesis, SAR, In silico Appraisal and Anti-Microbial Study of Substituted 2-aminobenzothiazoles Derivatives.

BACKGROUND: Antimicrobial resistance is a major global health problem, which is being rapidly deteriorating the quality of human health. Series of substituted N-(benzo[d]thiazol-2-yl)-2- (4-(6-fluorobenzo[d]isoxazol-3-yl) piperidin-1-yl)acetamide (3a-j) were synthesized from substituted N-(benzo[d]thiazol-2-yl)-2-chloroacetamide/bromopropanamide (2a-j) and 6-fluoro-3- (piperidin-4-yl)benzo[d]isoxazole (2) and further evaluated for their docking properties and antimicrobial activity. METHODS: All the synthesized compounds were characterized by FT-IR, NMR and Mass spectral analysis. All compounds were allowed to dock against different antimicrobial targets having PDB ID: 1D7U and against common antifungal target having PDB ID: 1EA1. RESULTS: The compounds 3d and 3h showed good activity against Methicillin-resistant Staphylococcus aureus (MRSA, resistance Gram-positive bacteria). All synthesized compounds showed good to moderate activity against selected bacterial and fungal microbial strains. If we compared the actual in-vitro antimicrobial activity and in silico molecular docking study, we found that molecules 3i and 3h were more potent than the others. CONCLUSION: Our current study would definitely pave the new way of designing and synthesis of more potent 2-aminobenzothiazoles derivatives.