TY - JOUR
T1 - Homopregnane-type ferrocene-steroid conjugates exhibit immunomodulatory activity
AU - Raičević, Vidak
AU - Jovanović, Ljiljana
AU - Rodić, Marko V.
AU - Stojanović, Nikola
AU - Ćulum, André Stephan
AU - Radulović, Niko
N1 - Publisher Copyright:
© 2025 Elsevier Inc.
PY - 2025/2
Y1 - 2025/2
N2 - 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.
AB - 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.
KW - Cyclic voltammetry
KW - Ferrocene
KW - Immunomodulatory activity
KW - Pregnanes
KW - X-ray crystallography
UR - http://www.scopus.com/inward/record.url?scp=85214103443&partnerID=8YFLogxK
U2 - 10.1016/j.bioorg.2025.108129
DO - 10.1016/j.bioorg.2025.108129
M3 - Article
AN - SCOPUS:85214103443
SN - 0045-2068
VL - 155
JO - Bioorganic Chemistry
JF - Bioorganic Chemistry
M1 - 108129
ER -