In vitro and In vivo Anticancer Activity of Semisynthetic Derivatives of Betulinic acid

A-ring modifications of betulinic acid isolated from Diospyros peregrina was carried out and the chemically modified derivatives were characterized by spectroscopic methods. Chemically modified betulinic acid analogues were subjected to molecular docking studies on topoisomerase-1 and were evaluated for in vitro and in vivo anticancer activity. In vitro anticancer studies revealed that among semisynthetic derivatives of betulinic acid the 2- benzylidene derivatives BE-6 and BE-7 as the most active compounds against HeLa and MDA-MB-435 cell lines. Compounds BE-6 and BE-7 exhibited apoptosis-mediated cell death and caused cell cycle arrest at the G0/G1 phase of HeLa cells. The in vivo Ehrlich ascites carcinoma model further confirms the antitumor efficacy BE-6 and BE-7. Molecular docking studies reveal that introduction of benzylidene group in the second position of betulinic acid has improved the binding affinity to topoisomerase-1. Further, the anticancer property of betulinic acid derivatives was in agreement with molecular docking results.