Synthesis and biological evaluation of novel steroidal 5α,8α-epidioxyandrost-6-ene-3β-ol-17-(O-phenylacetamide)oxime derivatives as potential anticancer agents

Abstract Inspired by the significant anti-cancer activity of our previously screened natural ergosterol peroxide (EP, 1 ), we synthesized and characterized a series of novel 5α,8α-epidioxyandrost-3β-ol-17-( O -phenylacetamide)oxime derivatives ( 9a – o ). The anti-proliferative activity of the synthesized compounds against human hepatocellular carcinoma cells (HepG2, Sk-Hep1) and human breast cancer cells (MCF-7, MDA-MB231) were investigated. Compounds 9d , 9f , 9h , 9j and 9m displayed good anti-proliferative activity (most IC 50 in vitro . Furthermore, fluorescence imaging showed that the designed coumarin- 9d conjugate ( 12 ) localized mainly in mitochondria, leading to enhanced anticancer activities over the parent structure.