Homopregnane-type ferrocene-steroid conjugates exhibit immunomodulatory activity

Abstract

Numerous compounds with useful biological activities were previously prepared by tethering ferrocene to natural product scaffolds. Some conjugates of ferrocene and steroids in particular were demonstrated to act as both potent and selective antiproliferative agents. Motivated by a lack of structural diversity in the pregnane series of conjugates, we performed chemical modifications of several naturally occurring progestogens, their biosynthetic precursors and chemically related derivatives so as to obtain conjugates 1-8, in which the steroid skeleton and ferrocene core are linked by the steroid sidechain. All compounds were characterized by 1D and 2D NMR, IR, UV-Vis, and HRMS; conjugate 7 was also analyzed by single-crystal X-ray diffraction. A cyclic voltammetric investigation of the electrochemical properties of 1-8 was performed. While none of the conjugates exhibited high cytotoxicity toward rat splenocytes, they were nevertheless found to enlist different types of immunomodulatory responses, most arising from the introduction of the ferrocene core.

Keywords: Cyclic voltammetry; Ferrocene; Immunomodulatory activity; Pregnanes; X-ray crystallography.