Synthesis, Antimycobacterial Evaluation and Docking Studies of Some 7-Methyl-5,6,7,8-tetrahydropyrido[4′,3′:4,5]thieno[2,3-d]pyrimidin-4(3H)-ones

Two series of 3-substituted-7-methyl-5,6,7,8-tetrahydropyrido[4′,3′:4,5] thieno[2,3-d]pyrimidin-4(3H)-one (6a–k) and 3-substituted-7,2-dimethyl-5,6,7,8-tetrahydropyrido[4′,3′:4,5]thieno[2,3-d]pyrimidin-4(3H)-one (7a–k) derivatives were synthesized and characterized using spectral data i.e., IR, 1H-, 13C-NMR, Mass and CHN elemental analyses. The synthesized compounds were evaluated for antibacterial activity against each of two strains of Gram-positive (Bacillus subtilis and Staphylococcus aureus) and Gram-negative (Escherichia coli and Klebsiella pneumoniae) bacteria and antimycobacterial activity screened against two strains i.e., Mycobacterium tuberculosis (MTB) H37Rv and an isoniazid-resistant clinical sample. Further to validate potentiality of our design was analyzed using molecular docking studies by taking crystal structure of MTB pantothenate synthetase (MTB-PS) (PDB: 3IVX). In this study, some compounds 6k (Minimum Inhibitory Concentration (MIC): MIC-22 µM), 7d (MTB: MIC-22 µM) and 7k (MTB: MIC-11 µM) showed potential antibacterial and antimycobacterial activities.