Benzothiazole and 2,3-dihydro-1,5-benzoxazepine Derivatives Demonstrate Antimicrobial Activity: An Antimicrobial and ADMET Study

Abstract

Antimicrobial resistance continues to be a serious public health threat globally, hence the continuous design of new clinical candidates with novel mechanisms of action. Heterocyclic drugs have been a hotspot in antibiotic research. Benzothiazole and 2,3-dihydro-1,5-benzoxazepine are anticancer derivatives. To follow up on their antimicrobial activity, the current work resynthesized 13 benzothiazole, benzimidazole, benzothiazepine, and 2,3-dihydro-1,5-benzoxazepine derivatives, followed by the evaluation of their antimicrobial and antitubercular activity against methicillinresistant Staphylococcus aureus (MRSA), Escherichia coli, Klebsiella pneumonia, Bacillus subtilis, Streptococcus mutans, Salmonella typhi, and Mycobacterium tuberculosis. In addition, in silico ADMET studies were performed on the compounds using the ADMET Laboratory 2.0 platform. The compounds were found to be active against all the bacterial strains except against S. mutans and S. typhi. 4-[(E)-2-(2-chlorophenyl) ethenyl]-2,2-dimethyl-2,3-dihydro-1,5-benzoxazepine (3) was found to be the most active against E. coli, 2,2,4-trimethyl-2,3-dihydrobenzoxazepine (12) the most active against MRSA, and 4-[(E)-2-(4-methoxyphenyl)ethenyl]-2,2-dimethyl-2,3-dihydro-1,5-benzoxazepine (6) the most active against Klebsiella pneumoniae. The compounds also showed moderate activity against M. tuberculosis. The ADMET analysis predicted largely drug-like properties of the compounds and their suitability as potential drugs. The synthesized compounds showed good activity against some of the selected organisms and, therefore, could be modified to improve their action as antimicrobial agents.