Title:One-Pot Syntheses and Enzyme Inhibition Studies of New C-28 Ester
Derivatives of Betulinic Acid
Volume: 22
Issue: 3
Author(s): Muhammad Shaiq Ali*, Sumera Shezadi, Azra Akbar, Humaira Zafar, Muhammad Imran Malik and Mahreen Lateef
Affiliation:
- H.E.J. Research Institute of Chemistry, ICCBS, University of Karachi, Karachi-75270, Pakistan
Keywords:
Betulinic esters, syntheses, enzyme inhibition, lipoxygenase activity, docking studies, butrylcholinesterase inhibition.
Abstract: Betulinic acid and its various synthetic derivatives have been reported to possess diverse
biological activities and some of these may serve as useful therapeutic agents for a variety of human
disorders. In this perspective, we have now developed convenient one-pot syntheses of new C-28
esters (2-7) of betulinic acid by esterification of the carboxylic moiety of betulinic acid (1) with various
alkylating agents. All the target compounds were subjected to enzyme inhibition studies to ascertain
their possible therapeutic utility. Compound 5 showed very potent lipoxygenase inhibitory activity
with an IC50 value of 13.2 μM, being much lower than the IC50 value of 22.4 μM of baicalein,
which was used as the standard. Butulinic acid itself and compound 6 also showed significant inhibitory
potential (IC50: 32.4 and 25.1 μM) against the same enzyme. The activities of both compounds 5
and 6 have been justified by intensive docking studies. Compounds 2 and 3 exhibited substantial inhibition
(IC50: 18.4 and 21.5 μM) against the enzyme butrylcholinesterase, compared to serine used as
the standard (IC50: 7.8 μM).
