Molecular modeling and biological investigation of novel s-triazine linked benzothiazole and coumarin hybrids as antimicrobial and antimycobacterial agents

AbstractAbstractA novel series of s-triazine linked benzothiazole and coumarin hybrids (6a-6d, 7a-7d, and 8a-8d) were synthesized and characterized by IR, NMR, and mass spectrometry. The compound's in vitro antibacterial and antimycobacterial activities were also evaluated. Remarkable antibacterial activity with MIC in the range of 12.5–62.5 μM and antifungal activity of 100–200 μM were demonstrated by in vitro antimicrobial analysis. Compounds 6b, 6d, 7b, 7d, and 8a strongly inhibited all bacterial strains, while 6b, 6c, and 7d had good to moderate efficacy against M. tuberculosis H37Rv. Synthesized hybrids are observed in the active pocket of the S. aureus dihydropteroate synthetase enzyme, according to a molecular docking investigations. Among the docked compounds, 6d had a strong interaction and a greater binding affinity, and the dynamic stability of protein-ligand complexes was examined using molecular dynamic simulation with various settings at 100 ns. The proposed compounds successfully maintained their molecular interaction and structural integrity inside the S. aureus dihydropteroate synthase, according to the MD simulation analysis. These in silico analyses supported the in vitro antibacterial results of compound 6d, which demonstrated outstanding in vitro antibacterial efficacy against all bacterial strains. In the quest for new antibacterial drug-like molecules, compounds 6d, 7b, and 8a have been identified as promising lead compounds.Communicated by Ramaswamy H. SarmaKeywords: 1,3,5-triazinebenzothiazolecoumarinbiological activityMD simulation AcknowledgmentsThe authors thank IISc, Bangalore, India, and CUG, Gujarat, India, for providing spectral data. The authors thank the Department of Chemistry of Sardar Vallabhbhai National Institute Technology, Surat, Gujarat, India, for providing all the facilities for the research work.Disclosure statementNo potential conflict of interest was reported by the authors.CRediT authorship contribution statementAjayrajsinh R. Zala: Conceptualization, methodology, writing original draft and editing; Dinesh Kumar, Uvais Razakhan: Methodology; Dhanji P. Rajani: Biological Analysis; Iqrar Ahmad: MD simulation and draft review; Harun Patel: Writing-review and editing; Premlata Kumari: Conceptualization, Supervision, Writing-review, and editing.Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.