Synthesis and antiproliferative evaluation of novel hydroxypropyl-ferrociphenol derivatives, resulting from the modification of hydroxyl groups

Abstract

As previously reported, the ferrocenyl derivative HO(CH2)3C(Fc) = C(C6H4OH)2 (2) shows an excellent cytotoxic effect against MDA-MB-231 (TNBC) cancer cell lines. Building on an analysis of this molecular framework, a series of novel hydroxypropyl-ferrociphenol derivatives with modified terminal hydroxyl groups were synthesized, and their antiproliferative activities against MDA-MB-231 cell lines were evaluated. Biological results showed that compound 8, whose terminal hydroxyl was protected by acetylation, exhibited the greatest cytotoxic effect among this series of hydroxypropyl derivatives. Furthermore, the impact of acetyl as a protecting group on the cytotoxicity of hydroxypropyl-ferrociphenol compounds by incorporating it at alkyl or phenyl hydroxyl positions of the core structure has been studied. Several of the compounds presented in this study revealed lipophilicity more suitable for formulation in lipid nanocapsules (LNCs) for subsequent in vivo studies. They also inhibit the cancer cell growth of MDA-MB-231 at a submicromolar IC50 value, providing an interesting potential for further development as innovative anticancer agents.