Betulin Acid Ester Derivatives Inhibit Cancer Cell Growth by Inducing Apoptosis through Caspase Cascade Activation: A Comprehensive In Vitro and In Silico Study
Paweł Pęcak, Marta Świtalska, Elwira Chrobak, Grzegorz Boryczka, Ewa Bębenek
Abstract
Betulin, or naturally occurring triterpene, possesses promising antiproliferative activity. To further explore this potential, thirty-eight betulin acid ester derivatives modified at the C-28 position were tested for antitumor activities. Four human cancer cell lines, MV4-11 (leukemia), A549 (lung), PC-3 (prostate), MCF-7 (breast) as well as the normal BALB/3T3 (mouse fibroblasts) cell line were examined using MTT and SRB assays. A few derivatives exhibited strong antiproliferative activity with IC50 values between 2 and 5 µM. Subsequent mechanistic studies revealed that some derivatives induced apoptosis by inducing caspase-3/7 activity. A strong structure–activity correlation of tested compounds has been proposed along with experimental and in silico pharmacokinetic properties.