Brevifoliol is an abeo-taxane isolated from the Taxus wallichiana needles; eighteen semisynthetic
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 the 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 the 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 the 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 compounds 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, with CC50 195.10 and 111.36, respectively towards the mouse bone marrow-derived
macrophages.
