Synthesis and anti-cancer activity of chiral tetrahydropyrazolo[1,5-a]pyridine-fused steroids

•Synthesis novel chiral heterocycle-fused steroids based on [8π + 2π] cycloadditions.•Biological evaluation of a new family of hexacyclic steroids as anti-cancer agents.•Conclusions regarding structure-activity relationships could be withdrawn.•A benzyl group at C24 is important to ensure cytotoxicity against EL4.

Regio- and stereoselective synthesis of novel chiral 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-fused steroids via [8π + 2π] cycloaddition of diazafulvenium methides with steroidal scaffolds is reported. The biological evaluation of the new family of hexacyclic steroids as anti-cancer agents was also carried out. Hexacyclic steroids bearing a benzyl group at C-22, derived from 16-dehydropregnenolone and 16-dehydroprogesterone, show considerable cytotoxicity against EL4 (murine T-lymphoma) in contrast with the corresponding C-22-unsubstituted derivatives showing low cytotoxicity. Thus, results indicate that the presence of the benzyl group is important to ensure cytotoxicity.

Graphical abstractDownload high-res image (194KB)Download full-size image