Facultad de Química y de Farmacia, Pontificia Universidad Católica de Chile, Santiago 6094411, Chile.
Facultad de Química y de Farmacia, Pontificia Universidad Católica de Chile, Santiago 6094411, Chile.
Bioorg Chem. 2021 Jun;111:104823. doi: 10.1016/j.bioorg.2021.104823. Epub 2021 Mar 12.
Herein, the design and synthesis of new 2-phenyl(pyridinyl)benzimidazolequinones and their 5-phenoxy derivatives as potential anti-Trypanosoma cruzi agents are described. The compounds were evaluated in vitro against the epimastigotes and trypomastigote forms of Trypanosoma cruzi. The replacing of a benzene moiety in the naphthoquinone system by an imidazole enhanced the trypanosomicidal activity against Trypanosoma cruzi. Three of the tested compounds (11a-c) showed potent trypanosomicidal activity and compound 11a, with IC of 0.65 μM on the trypomastigote form of T. cruzi, proved to be 15 times more active than nifurtimox. Additionally, molecular docking studies indicate that the quinone derivatives 11a-c could have a multitarget profile interacting preferentially with trypanothione reductase and Old Yellow Enzyme.
本文描述了新型 2-苯基（吡啶基）苯并咪唑醌及其 5-苯氧基衍生物作为潜在抗 Trypanosoma cruzi 药物的设计和合成。这些化合物在体外对 Trypanosoma cruzi 的滋养体和变形体进行了评估。将萘醌系统中的苯环部分替换为咪唑，增强了对 Trypanosoma cruzi 的杀变形体活性。测试的三种化合物（11a-c）表现出很强的杀变形体活性，化合物 11a 对 T. cruzi 的变形体形式的 IC 为 0.65 μM，比硝呋替莫活性高 15 倍。此外，分子对接研究表明，醌衍生物 11a-c 可能具有多靶点特性，优先与 trypanothione 还原酶和 Old Yellow Enzyme 相互作用。
