Synthesis, <i>In vitro</i> Antibacterial and Antimycobacterial Activity and DockingStudy of Thieno(3,2-e)(1,2,4)triazolo(1,5-c)pyrimidines

Background: Emergence of drug resistance and severe side effects with current an-titubercular drugs urges the development of more efficacious and safer new agents. The present study focused on this direction to develop new hetero-fused pyrimidines as potential antitubercu-lar agents. Objective: The objective of the study was to synthesize and assess the antibacterial and antimy-cobacterial activity of novel 1,2,4-triazole ring bearing hetero-fused thienopyrimidines (6a-j &amp; 7a-j). Also to evaluate the binding pattern of synthesized molecules at the target site and study their ADME properties by in silico tools. Methods: Two series of hetero fused thienopyrimidines (6a-j &amp; 7a-j) were synthesized and tested for their antibacterial potentiality against B. subtilis, S. aureus, E. coli, and K. pneumonia. Com-pounds with potential antibacterial activity were further tested for their antitubercular activity against Mycobacterium tuberculosis (MTB) H37Rv and an isoniazid (INH)-resistant clinical sam-ple of MTB using broth microdilution method. The binding efficacy at the enzyme site was eval-uated by the molecular docking study using pantothenate synthetase (MTB-PS) (PDB: 3IVX) as the target protein. Further, in silico ADME properties of title compounds were explored by Swiss ADME online tools. Results: In this study, few compounds were found promising in exhibiting potent inhibitory ac-tivity against E. coli and MTB. Among these compounds, 6h (MTB: MIC-17.13±0.88 μM) and 6i (MTB: MIC-17.55±0.72 μM) displayed significant antimycobacterial activity. The molecular docking results suggested the efficient binding of biologically potential molecules. Conclusion: Compounds bearing N-benzyl moiety at the core nucleus with a p-nitro aryl side chain (6h) exhibited significant antitubercular activity. In silico studies showed effective binding at the target site and also indicated good compatibility in ADME properties.