Synthesis of 4-hetero-16α,17α-cyclohexanopregnanes and evaluation of their cytotoxicity against the HeLa cell line

Abstract

The oxidation of the ring A of 16α,17α-cyclohexanoprogesterone gave 5-oxo-A-nor-3,5-secopregnan-3-oic acid. The subsequent ring A closure in the latter compound upon treatment with sodium acetate in Ac₂O afforded 4-oxasteroid. The reaction with ammonium acetate in acetic acid produced 4-azasteroid. Antiproliferative activity of the resulting steroids against cervical cancer HeLa cells and the in vitro binding to the progesterone receptor were studied. The compounds cause a statistically significant decrease in viability of cervical cancer HeLa cells, having no effect on normal skin fibroblasts. The tested steroids show very low binding to the rat uterine progesterone receptor.