Exploring the Potential of Sulfur Moieties in Compounds Inhibiting Steroidogenesis

Exploring the Potential of Sulfur Moieties in Compounds Inhibiting Steroidogenesis

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 reveale...

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Bibliographic Details
Published in:Biomolecules (Basel, Switzerland) Vol. 13; no. 9; p. 1349
Main Authors: Wróbel, Tomasz M, Sharma, Katyayani, Mannella, Iole, Oliaro-Bosso, Simonetta, Nieckarz, Patrycja, Du Toit, Therina, Voegel, Clarissa Daniela, Rojas Velazquez, Maria Natalia, Yakubu, Jibira, Matveeva, Anna, Therkelsen, Søren, Jørgensen, Flemming Steen, Pandey, Amit V, Pippione, Agnese C, Lolli, Marco L, Boschi, Donatella, Björkling, Fredrik
Format: Journal Article
Language:English
Published: Basel MDPI AG 01-09-2023
MDPI
Subjects:
AKR1C3
Aldo-keto reductase
Androgens
Biosynthesis
Chromatography
CYP17A1
Cytochrome P450
enzyme inhibition
Enzymes
Health aspects
Medical prognosis
Nitrogen
Oxidoreductase
Phenols
Prevention
Prostate cancer
Steroid hormones
Steroidogenesis
Sulfur
Poland
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Summary: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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ISSN:2218-273X
2218-273X
DOI:10.3390/biom13091349