Targeting the antigen 85 complex of Mycobacterium tuberculosis: A three-fold validation of antimycobacterial activity of Centella asiatica.

INTRODUCTION: One of the biggest challenges associated with tuberculosis is the emerging drug resistance which emphasizes the need of alternative therapeutic approaches. In recent years, multitargeting approach for TB therapy has garnered considerable attention. The Antigen85 complex of proteins represent key enzymes which are involved in Mtb cell wall biosynthesis. This study aims at investigating the antimycobacterial effects of Centella asiatica and its two compounds - asiatic acid and quercetin against these three proteins and validate them as multi targets for drug targeting.

METHODS: Three-fold validation approach included in-silico studies, in-vitro inhibitory studies against MtbH37Ra strain and inhibition studies against recombinant enzymes.

RESULTS: Displaying good bioavailability, asiatic acid and quercetin exhibited favorable binding affinities. Disruption of the integrity of the cell membrane of MtbH37Ra was observed through electron microscopy and flow cytometry. Both compounds and extract showed inhibitory activity against the enzymes and microorganism and were found to act synergistically in conjunction with isoniazid. Asiatic acid demonstrated bactericidal activity. The reduced reaction rate of the recombinant enzymes implied their function and activity were hampered, which was confirmed through a fluorometric assay.

CONCLUSION: These results highlight the potential of asiatic acid and quercetin as multitarget inhibitors of the Mtb Antigen85 complex.