Brevifoliol and its Analogs: A New Class of Antitubercular Agents.

Brevifoliol is an abeo-taxane isolated from the Taxus wallichiana needles, eighteen semi-synthetic esters derivatives of brevifoliol were prepared by Steglich esterification and screened for their anti-tubercular potential against Mycobacterium tuberculosis H37Ra avirulent strain. The 3-[chloro (7)] and 3, 5-[dinitro (8)] benzoic acid ester derivatives were most active (MIC 25 ug/ml) against the pathogen. Further, in silico docking studies of the active derivative 7 with mycobacterium enzyme inhA (enoyl-ACP reductase) gave a LibDock score of 152.68 and binding energy of -208.62 and formed three hydrogen bonds with SER94, MET98, and SER94. Similarly, when derivative 8 docked with inhA, it gave a LibDock score of 113.55 and binding energy of -175.46 and formed a single hydrogen bond with GLN100 and Pi-interaction with PHE97. On the other hand the known standard drug isoniazid (INH) gave a LibDock score of 61.63, binding energy of -81.25 and formed one hydrogen bond with ASP148. These molecular docking results and the way of binding pattern indicated that compound 7 and 8 bound well within the binding pocket of inhA and showed a higher binding affinity than the known drug Isoniazid. Additionally, both the derivatives (7 and 8) showed no cytotoxicity towards the healthy liver cell lines CHANG.