Coumarin hybrids: dual-target candidates for future antimicrobial and antitubercular therapies.

Abstract

Aims: This study aimed to synthesize, characterize, and evaluate the antimicrobial and antitubercular activities of two novel series of coumarin-based derivatives (Series 5 and Series 9), focusing on their structure-activity relationship (SAR) and molecular docking interactions with key bacterial enzymes.

Materials & methods: Series 5 (5a-5j) and Series 9 (9a-9t) compounds were synthesized and characterized using spectroscopic techniques. Their antimicrobial and antitubercular activities were evaluated against Mycobacterium tuberculosis, Staphylococcus aureus, Bacillus subtilis, and E. coli. IC₅₀ values were determined, and molecular docking studies were conducted to assess binding interactions with M. tuberculosis enoyl-ACP reductase (InhA) and E. coli DNA gyrase B.

Results: Series 5 compounds exhibited moderate activity, with 5f, 5 g, 5i, and 5j showing notable inhibition. Series 9 derivatives displayed superior dual-target inhibition, with 9t, 9c, 9a, 9b, and 9p achieving >90% inhibition against S. aureus and B. subtilis. The lowest IC₅₀ against M. tuberculosis was observed for 9c (1.50 µg/mL), followed by 9a (2.84 µg/mL) and 9b (2.73 µg/mL). Molecular docking confirmed strong binding interactions, correlating with observed biological activities.

Conclusions: Series 9 compounds, particularly 9t, 9c, and 9a, demonstrate high potential as dual-target antimicrobial drug candidates. Further optimization may enhance their therapeutic efficacy.