A In Silico Evaluation of Leucaena leucocephala Seed Phytochemicals as Potential inhA Inhibitors Against Tuberculosis:

Abstract

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains one of the world’s most concerning infectious diseases due to rising incidence and growing drug resistance. The enoyl-acyl carrier protein reductase (InhA), a key enzyme in the fatty acid synthase II pathway, is a validated target for anti-TB drug discovery as it catalyzes mycolic acid biosynthesis in the Mtb cell wall. This study aimed to evaluate the inhibitory potential of bioactive compounds derived from Leucaena leucocephala seeds against the InhA protein using in silico molecular docking. A total of 73 phytochemicals were screened for drug-likeness and toxicity profiles, resulting in the selection of 11 compounds for docking analysis. Catechin exhibited the strongest binding affinity (−8.2 kcal/mol) with diverse hydrogen bonding and hydrophobic interactions, surpassing the reference drug isoniazid (−5.8 kcal/mol). Diethyl phthalate (−7.5 kcal/mol) and several linoleic acid derivatives (−6.0 to −6.6 kcal/mol) also demonstrated favorable interactions with the InhA active site. The study suggests that phytochemicals from L. leucocephala seeds may offer safe, natural compounds with potential relevance to anti-tuberculosis research and could serve as a basis for further in vitro and in vivo exploration.