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Abstract

A series of side chain modified structurally diverse 3,4-dihydro-2H-benzo[b][1,4]-oxazine-2-carboxylic acid derivatives were synthesized and characterized by IR, 1H NMR, 13C NMR and mass spectral study. All the newly synthesized compounds were examined for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Ra. The synthesized compounds exhibited minimum inhibitory concentration (IC50) ranging from 5.98 to >30 (μg/mL) against MtbH37Ra. Among the screened compounds, compounds 5a, 5c, 5d, 5f, 5g, 5h, 5I, 5j exhibited IC50 as 10.42, 11.81, 18.79, 5.98, 19.21, 24.81 and 14.81 μg/mL, respectively. The antibacterial screening study of these compounds was conducted against four different bacteria to asses there selectivity towards MTB. The antibacterial screening of all the synthesized compounds was conducted against four bacterial strains (Gram-negative strains: E.coli and S.aureus; Gram-positive strains: P. aeruginosa and B.subtilis. The compounds 5a, 5b, 5c, 5e and 5j showed higher antibacterial activity up to 7-25 μg/mL. Furthermore, molecular docking studies revealed the binding modes of the compounds in the binding site of the good agreement with the in vitro antitubercular screening. The compounds 5a, 5c and 5f with free energy of binding lower than -9.0 Kcal/mol binds more favourably at the binding site of panC as compared to other compounds. Specifically, the compound 5f with free energy of binding -9.6 Kcal/mol is indeed found more active in docking study as well as in the in vitro antitubercular screening. These findings open the possibility for potential lead for antituberculosis chemotherapy.

Keywords

Benzooxazines Antitubercular agents

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S. Tambe, M., Gadhe, S., Choudhari, A., Sarkar, D., N. Sangshetti, J., & B. Patil, R. (2020). Synthesis and Biological Evaluation of 3,4-Dihydro-2H-benzo[b][1,4]-oxazine-2-carboxylic Acid Derivatives as Antitubercular Agents. Asian Journal of Organic & Medicinal Chemistry, 5(2), 138–148. https://doi.org/10.14233/ajomc.2020.AJOMC-P261
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