Communications

New abiraterone analogue with atypical position of N-heterocyclic substituent: synthesis, crystal structure and CYP17A1/CYP3A4 binding affinity

E. V. Nurieva^a, E. V. Britikova^b, A. V. Sydoriuk^a, T. A. Antonenko^a, A. V. Mamaeva^a, N. A. Zefirov^c, A. V. Zazdravnykh^a, V. A. Tafeenko^a, E. V. Bocharov^d, V. V. Britikov^b, E. R. Milaeva^a, O. N. Zefirova<sup>a

a</sup> Department of Chemistry, M. V. Lomonosov Moscow State University, 119991 Moscow, Russian Federation
^b Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus, 220084 Minsk, Belarus
^c Institute of Physiologically Active Compounds, Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences, 142432 Chernogolovka, Moscow Region, Russian Federation
^d M. M. Shemyakin–Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russian Federation

Abstract: Atypical steroid-like analogue of abiraterone, an inhibitor of androgen biosynthesis, was synthesized and characterized by X-ray diffraction analysis. The in vitro study of the compound by differential spectrophotometric titration revealed its ability to bind to truncated CYP17A1 (∆2–19 variant) in a type II fashion through nitrogen coordination with lower affinity than that of abiraterone, but still in nanomolar concentration range (KD ≈ 187 nm). The significant spectral response (∆A_max) value suggests that the new compound effectively targets the conformational ensemble of CYP17A1 accessible for ligand binding.

Keywords: steroids, abiraterone, rearrangement of steroid core, X-ray analysis, cytochrome P450 17A1 inhibitors, prostate cancer.

Received: 19.08.2025
Accepted: 02.10.2025

Language: English

DOI: 10.71267/mencom.7900