Novel Endoperoxide Steroid Derivatives Containing Thiazole Moiety as Potential Antitumor Agents: Design, Synthesis, and Cytotoxic Evaluation

Abstract

As part of the search for new steroid substances with potential application in oncology, a series of endoperoxide steroid derivatives (7a-n) containing a thiazole system were synthesized and evaluated for their cytotoxicities in four tumor cell lines. Among them, compound 7h exhibited the most significant cytotoxic activity against HepG2 cells (IC50  =  4.54 μM), being more potent than ergosterol peroxide. Furthermore, 7h was able to promote apoptosis in HepG2 cells and decrease the mitochondrial membrane potential, accompanied by activating the expression of cytochrome c, caspase-9, caspase-3, and Bax, while Bcl-2 expression was suppressed. The molecular mechanism may refer to the mitochondrial apoptotic pathway. On the whole, the above results incentivize the further study of 7h derivatives as potent anticancer agents.