Steroidal Ferrocenes as Potential Enzyme Inhibitors of the Estrogen Biosynthesis

Herman, Bianka Edina and Gardi, János and Julesz, János and Tömböly, Csaba and Szánti-Pintér, Eszter and Fehér, Klaudia and Skoda-Földes, Rita and Szécsi, Mihály (2020) Steroidal Ferrocenes as Potential Enzyme Inhibitors of the Estrogen Biosynthesis. BIOLOGIA FUTURA, 71 (3). pp. 249-264. ISSN 2676-8615 (print); 2676-8607 (online)

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Abstract

The potential inhibitory efect 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 ferrocenylalkynes using our efcient methodology published previously. Inhibition of human aromatase, steroid sulfatase (STS) and 17β-hydroxysteroid dehydrogenase type 1 (17β-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 17β-estradiol exerted outstanding inhibitory efect and experiments demonstrated a key role of the ferrocenyl moiety in the enhanced binding afnity. Submicromolar IC50 and Ki parameters enroll these compounds to the group of the most efective 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 17β-estradiol in target tissues.

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