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 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 effect and experiments demonstrated a key role of the ferrocenyl moiety in the enhanced binding affinity. Submicromolar IC₅₀ and K_i 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 17β-estradiol in target tissues.

研究了多种三唑基-二茂铁类固醇对雌激素生物合成关键酶的潜在抑制作用。使用我们之前发表的有效方法，通过铜催化的甾体叠氮化物和二茂铁基炔烃的环加成合成测试化合物。通过体外放射性底物孵育研究了对人芳香化酶、类固醇硫酸酯酶 (STS) 和 17β-羟基类固醇脱氢酶 1 型 (17β-HSD1) 活性的抑制作用。一些测试化合物被发现是 STS 的有效抑制剂。在 C-2 上带有二茂铁侧链的化合物表现出可逆的抑制作用，而 C-16 和 C-17 衍生物表现出对酶的竞争性不可逆结合机制。17β-雌二醇的 17α-三唑基-二茂铁衍生物发挥出色的抑制作用，实验证明二茂铁基部分在增强结合亲和力中起关键作用。亚微摩尔集成电路₅₀和K _i参数将这些化合物纳入迄今为止公布的最有效的 STS 抑制剂组。甾体二茂铁的 STS 抑制潜力可能导致开发能够抑制靶组织中 17β-雌二醇原位生物合成的新型化合物。