Abstract

Background: The modification of steroidal structure is commonly used to change the biological activity of steroids in medicinal chemistry. Some steroids containing heterocycles exhibit distinct cytotoxicity against various cancer cell lines and have been receiving wide attention over the years by medicinal chemists for drug discovery.

Methods: Using pregnenolone and stigmasterol as starting materials, via different chemical reaction, two series of heterosteroids with side chain of 20- and 22-hydrazone aromatic cycles or heterocycles in their structures were synthesized and characterized by IR, NMR and HRMS. The antiproliferative activity of the compounds in vitro was evaluated against human HT-29, HeLa, Bel 7404 and SGC 7901 cancer cells by MTT assays.

Results: The steroidal compounds with side chain of 20-hydrazone aromatic cycles or heterocycles exhibited distinct cytotoxicity. However, analogues with the side chain of 22-hydrazone resulted in a dramatic decrease of the cytotoxicity. The result of Annexin V assay showed that the 20-hydrazone compounds were potent apoptotic inducers against these carcinoma cells.

Conclusion: Steroidal compounds with the side-chain of 20-hydrazone aromatic heterocycles exhibit distinct antiproliferative activity in vitro. However, the compounds with the side-chain of 22-hydrazone aromatic heterocycle decreased the cytotoxicity of the compounds.

Keywords: Antiproliferative activity, cytotoxicity, hydrazones, pregnenolone, 22-seco-stigmastan-22-al.

Graphical Abstract