Synthesis of 5α,8α‐Ergosterol Peroxide 3‐Carbamate Derivatives and a Fluorescent Mitochondria‐Targeting Conjugate for Enhanced Anticancer Activities

Abstract Inspired by the significant anticancer activity of our previously screened natural ergosterol peroxide ( 1 ), we synthesized and characterized a series of novel ergosterol peroxide 3‐carbamate derivatives. The antiproliferative activities of the synthesized compounds against human hepatocellular carcinoma cells (HepG2, SK‐Hep1) and human breast cancer cells (MCF‐7, MDA‐MB231) were investigated. 5α,8α‐Epidioxyergosta‐3‐yl‐(piperazine‐1)carbamate ( 3 d ) and 5α,8α‐epidioxyergosta‐3‐yl‐(piperidin‐4‐methylamine)carbamate ( 3 f ) and their hydrochloride salts exhibited significant in vitro antiproliferative activities against the tested tumor cell lines, with IC 50 values ranging from 0.85 to 4.62 μ m . Furthermore, fluorescent imaging showed that the designed coumarin– 3 d conjugate ( 5 ) localized mainly in mitochondria, leading to enhanced anticancer activities over the parent structure 1 . As a whole, it appeared that substituent changes at the C3 position could serve as a promising launch point for further design of this type of steroidal anticancer agent.