Design, synthesis and biological evaluation of novel 5α, 8α-endoperoxide steroidal derivatives with hybrid side chain as anticancer agents.

• Synthesis of peroxide steroidal derivatives with isatin/indole side chain. • Compounds 7g and 7l exhibited significant anti-proliferative activities. • Compound 7g induced HepG2 cell apoptosis, inhibited cycle progression and colony growth. A series of novel 5α, 8α-endoperoxide steroidal hybrid derivatives containing isatin or indole substituents on the C-17 side chain were synthesized and characterized. The preliminary anti-proliferative activity of the compounds against HepG2, MCF-7, HT-29 and HeLa cell lines were investigated. Compounds 7g and 7l displayed significant anti-proliferative activity in vitro against HepG2 and Hela cells, with IC 50 values lower than 8 μM. Furthermore, the biological functions of 7g were examined by flow cytometry and colony analysis. The results showed that 7g could induce HepG2 cell apoptosis, inhibited cell cycle progression, and colony growth. The studies indicated that structural modification at C-17 position could be a promising launch point for design steroidal anticancer agents. [ABSTRACT FROM AUTHOR]