Ferrocene-steroid conjugates: Synthesis, structure and biological activity

Four ferrocene-steroid conjugates (steroid = 3 alpha-hydroxy androstan-17-one (androsterone, 3 beta-hydroxy androstan-17-one (trans-androsterone), 3 beta-hydroxy pregn-5-en-18-one (pregnenolone) and 3 beta-hydroxy dehydroandrostan-17-one (dehydroepiandrosterone, DHEA)) were synthesized and structurally characterized by analytical methods. The molecular structures of 16-ferrocenylidene-3 alpha-hydroxy androstan-17-one, 1, 16-ferrocenylidene-3 beta-hydroxy androstan-17-one, 2, and 21-ferrocenylidene-3 beta-hydroxy pregn-5-en-20-one, 3, were determined by single crystal X-ray diffraction techniques. The crystallographic data confirmed the aldol condensation was achieved in C-16 for 1 and 2, and C-21 in 3. 1 and 2 showed ferrocene is positioned in the beta face of the steroid while for 3 is positioned between alpha and beta faces. The anti-proliferative activity of these conjugates was determined on colon cancer HT-29 and breast cancer MCF-7 cell lines. The conjugates displayed moderate to high anti-proliferative activity on both cell lines, 16-ferrocenylidene-3 alpha-hydroxy androstan-17-one being the most active on HT-29. (C) 2017 Elsevier B.V. All rights reserved.