Recent Updates on Anticancer Activity of Betulin and Betulinic Acid Hybrids (A Review)
Jun Wang, Yu-min Shi
Abstract
Abstract The frequency of human being suffering from cancer is increasing annually throughout the world, but treatment of cancer is becoming more complex in recent years due to the multidrug resistance, creating an urgent demand for novel chemotherapeutics. Betulin and betulinic acid as lupane-type pentacyclic triterpenes distributed ubiquitously in the plant kingdom. Betulin and betulinic acid derivatives could hold the anticancer effects through different mechanisms, inclusive of induction of apoptosis and autophagy, antiangiogenesis, inhibition of invasion and migration, cell cycle arrest and multidrug resistance reversal. Notably, betulin and betulinic acid hybrids have been recently identified as promising candidates to explore novel anticancer chemotherapeutics since these derivatives could circumvent multidrug resistance, reduce the toxicity, and improve the efficacy. This review outlines the research progress regarding the anticancer potential of betulin and betulinic acid hybrids from 2012 to 2022, and the structure–activity relationship and mechanisms of action were also discussed.