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C16 and C17 Substituted Derivatives of Pregnenolone and Progesterone as Inhibitors of 17α‐Hydroxylase‐C17, 20‐lyase: Synthesis and Biological Evaluation
Author(s) -
Haidar Samer,
Hartmann Rolf W.
Publication year - 2003
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.200290006
Subject(s) - pregnenolone , lyase , enzyme , chemistry , biochemistry , biosynthesis , reductase , cyp17a1 , active site , steroid , stereochemistry , hormone
17α‐Hydroxylase‐C17, 20‐lyase (P450 17, CYP 17) is a key enzyme in androgen biosynthesis and a target for the treatment of prostate cancer. In order to find novel inhibitors for this enzyme, several compounds bearing different moieties able to complex with the heme iron located in the active site of the enzyme were synthesized. The moieties were introduced into the 16‐position of pregnenolone and progesterone. Their inhibitory activities toward human and rat CYP 17 were determined and compared to the activities of the corresponding 17‐substituted compounds. It became apparent that the 16‐substituted compounds were less active than the parent compounds: they were either moderate or poor inhibitors of the target enzyme. Tested for inhibition of human 5α‐reductase 1 and 2 — a target for the treatment of benign prostatic hyperplasia (BPH) — the title compounds showed some inhibitory activity.