Synthesis, NMR characterization and cytotoxic activity of hybrid spirostanic sapogenins-estradiol dimers

Four hybrid steroid dimers were obtained by BF₃·Et₂O-catalyzed aldol condensation of acetylated steroid sapogenins with 2-formyl-estradiol diacetate. The structures of the obtained dimers were unambiguously established by NMR. The hybrid dimers 9a (IC₅₀ 18.37 μM) and 9c (IC₅₀ 9.4 μM) with the 5α configuration at the A/B rings junction showed the higher cytotoxicity against HeLa, with selectivity index of 4.36 and 11.8 respectively. The presence of a carbonyl function at position C-12 produced the highest cytotoxic effect, which is in line with our previous reports.