Molecular docking interactions with mycobacterial ATP and polyketide -13 synthase enzymes of phytoconstituents isolated from entada abyssinica stem bark

Abstract

The search for novel therapies for tuberculosis continues due to the emergence of resistant strains, adverse drug reactions, and potential drug-drug interactions of antitubercular drugs. This study was undertaken to identify compounds from Entada abyssinica, a plant used by herbalists in East Africa for the management of symptoms of tuberculosis. An extract of shade-dried E. abyssinica stem bark was prepared by maceration in a mixture of acetone and methanol in the ratio of 3:2. Column and thin layer chromatography were used to isolate pure compounds. The structures of the compounds were elucidated using nuclear magnetic resonance and infrared spectroscopy. The compounds were further studied using in silico tools to predict their binding affinities, descriptors of pharmacokinetics, and toxicity. Seven known compounds: 2,3-dihydroxypropyltriacontanoate (1), 1',26'-bis-(2,3- dihydroxypropyl) hexacosanedioate (2), stigmasterol 3-O--D-glucopyranoside (3), sitosterol 3-O-- D-glucopyranoside (4), Spinasterol 3-O--D-glucopyranoside (5), stigmasterol (6) and spinasterol (7) were isolated. Compounds 1 and 2 had better binding affinities (-27.7374 and -28.5726 Kcal/mol) than the bedaquiline (-22.9042 Kcal/mol) for ATP. All isolated compounds had better binding affinities (between -21.4357 and -18.7809 Kcal/mol) than isoniazid (-10.8307 Kcal/mol) for polyketide-13 synthase enzymes. The compounds showed variable but promising pharmacokinetic properties with minimum toxicity. E. abyssinica stem bark contains phytochemicals with promising antimycobacterial activity via inhibition of the ATP and polyketide-13 synthase enzymes. In vitro and in vivo studies are recommended to validate the predicted antimycobacterial activity as well as the pharmacokinetics and toxicity profiles.