Anti-tuberculosis potential of bruceine: An in silico approach

Abstract

Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis. The bacterial enzyme pantothenate synthetase (PS) catalyzes the synthesis of pantothenate, a precursor of coenzyme A. Hence, targeting PS is a potential mechanism in the development of anti-tuberculosis drugs. Bruceine, a highly oxygenated natural quassinoid molecule, is isolated from plants of the Simaroubaceae family. The anti-tuberculosis potential of eleven bruceine (A, B, C, D, E, G, H, I, J, K and L) has been investigated by in silico approach. The molecular docking (AutodockVina) and drug-likeness (Lipinski’s rule of five) analyses identified bruceine D as a potential inhibitor. Further, it has shown six hydrogen bond interactions with the key amino acids residues of the target protein, Tyr82, His135, Lys160 and Asp161. The ring-A and -D has contributed two hydrogen bonds, while one each from ring-C and -E. The results reveal that bruceine D possesses druglikeness property and binding energy of -9.3 kcal/mol. The binding score similar to pantoyl adenylate suggests chemical modifications to enhance the protein inhibition potency. Bruceine D has a great potential to inhibit PS and could contribute to the tuberculosis drug discovery process.