Steroidal ferrocenes as potential enzyme inhibitors of the estrogen biosynthesis.
Biol Futur
; 71(3): 249-264, 2020 Sep.
Article
em En
| MEDLINE
| ID: mdl-34554507
ABSTRACT
The potential inhibitory effect of diverse triazolyl-ferrocene steroids on key enzymes of the estrogen biosynthesis was investigated. Test compounds were synthesized via copper-catalyzed cycloaddition of steroidal azides and ferrocenyl-alkynes using our efficient methodology published previously. Inhibition of human aromatase, steroid sulfatase (STS) and 17ß-hydroxysteroid dehydrogenase type 1 (17ß-HSD1) activities was investigated with in vitro radiosubstrate incubations. Some of the test compounds were found to be potent inhibitors of the STS. A compound bearing ferrocenyl side chain on the C-2 displayed a reversible inhibition, whereas C-16 and C-17 derivatives displayed competitive irreversible binding mechanism toward the enzyme. 17α-Triazolyl-ferrocene derivatives of 17ß-estradiol exerted outstanding inhibitory effect and experiments demonstrated a key role of the ferrocenyl moiety in the enhanced binding affinity. Submicromolar IC50 and Ki parameters enroll these compounds to the group of the most effective STS inhibitors published so far. STS inhibitory potential of the steroidal ferrocenes may lead to the development of novel compounds able to suppress in situ biosynthesis of 17ß-estradiol in target tissues.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Triazóis
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Compostos Ferrosos
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Esteril-Sulfatase
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11-beta-Hidroxiesteroide Desidrogenase Tipo 1
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Inibidores da Aromatase
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Metalocenos
Tipo de estudo:
Evaluation_studies
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article