Universidade Federal Fluminense, Departamento de Tecnologia Farmacêutica, Faculdade de Farmácia, Santa Rosa, CEP 24241-002 Niterói, RJ, Brazil.
Universidade Federal Fluminense, Instituto de Química, Departamento de Química Orgânica, Campus do Valonguinho, CEP 24020-150 Niterói, RJ, Brazil.
Bioorg Chem. 2021 Nov;116:105250. doi: 10.1016/j.bioorg.2021.105250. Epub 2021 Aug 11.
1,2,3-triazole heterocycles stand out in medicinal chemistry for having great structural diversity and bioactivities. In this study, two series of triazoles were synthesized. One was obtained by the 1,3-dipolar cycloaddition reaction between ethyl cyanoacetate and several phenyl azides forming 1H-1,2,3-triazoles and the other by rearrangement of Dimroth forming and 2H-1,2,3-triazoles. Both series were shown to be active against the epimastigote form of Trypanosoma cruzi. The 1,2,3-triazoles 16d (S.I. between 100 and 200), 17d and 16f (S.I. > 200) were the most active compounds and capable of breaking the plasma membrane of trypomastigotes acting on CYP51 and inhibiting ergosterol synthesis. Candidate 16d exhibited the best and most favorable profile when interacting with CYP51.
1,2,3-三唑杂环在药物化学中因其具有丰富的结构多样性和生物活性而备受关注。在本研究中，我们合成了两个系列的三唑化合物。其中一个系列是通过乙基氰乙酸酯与几个苯基叠氮化物的 1,3-偶极环加成反应得到的 1H-1,2,3-三唑化合物，另一个系列是通过 Dimroth 重排形成的 2H-1,2,3-三唑化合物。这两个系列的化合物均表现出对克氏锥虫的前鞭毛体形式的活性。1,2,3-三唑化合物 16d（SI 在 100 到 200 之间）、17d 和 16f（SI>200）是最具活性的化合物，能够破坏游离体的质膜，作用于 CYP51 并抑制麦角固醇合成。候选化合物 16d 在与 CYP51 相互作用时表现出最佳和最有利的特性。
