Exploring the Potential of Sulfur Moieties in Compounds Inhibiting Steroidogenesis
2023
Tomasz M. Wróbel | Katyayani Sharma | Iole Mannella | Simonetta Oliaro-Bosso | Patrycja Nieckarz | Therina Du Toit | Clarissa Daniela Voegel | Maria Natalia Rojas Velazquez | Jibira Yakubu | Anna Matveeva | Søren Therkelsen | Flemming Steen Jørgensen | Amit V. Pandey | Agnese C. Pippione | Marco L. Lolli | Donatella Boschi | Fredrik Björkling
This study reports on the synthesis and evaluation of novel compounds replacing the nitrogen-containing heterocyclic ring on the chemical backbone structure of cytochrome P450 17α-hydroxylase/12,20-lyase (CYP17A1) inhibitors with a phenyl bearing a sulfur-based substituent. Initial screening revealed compounds with marked inhibition of CYP17A1 activity. The selectivity of compounds was thereafter determined against cytochrome P450 21-hydroxylase, cytochrome P450 3A4, and cytochrome P450 oxidoreductase. Additionally, the compounds showed weak inhibitory activity against aldo-keto reductase 1C3 (AKR1C3). The compounds’ impact on steroid hormone levels was also assessed, with some notable modulatory effects observed. This work paves the way for developing more potent dual inhibitors specifically targeting CYP17A1 and AKR1C3.
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