One-Pot Syntheses and Enzyme Inhibition Studies of New C-28 Ester Derivatives of Betulinic Acid

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 mu M, being much lower than the IC50 value of 22.4 mu M 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 mu M) 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 mu M) against the enzyme butrylcholinesterase, compared to serine used as the standard (IC50: 7.8 mu M).