喹喔啉
无鞭毛体
克鲁兹锥虫
化学
利什曼原虫
墨西哥利什曼原虫
生物活性
IC50型
恰加斯病
体外
EC50型
杀锥虫剂
结构-活动关系
立体化学
生物化学
布氏锥虫
有机化学
生物
免疫学
寄生虫寄主
万维网
计算机科学
基因
作者
Juliana Cogo,Vanessa Kaplum,Diego Pereira Sangi,Tânia Ueda-Nakamura,Arlene G. Corrêa
标识
DOI:10.1016/j.ejmech.2014.11.018
摘要
Quinoxalines belong to the N-containing heterocyclic compounds that stand out as having promising biological activity due to their privileged scaffold. In this work, we report the synthesis, antileishmanial, and antitrypanosomal properties of 46 new 2,3-disubstituted quinoxaline and 40 previously reported derivatives. Among all of the compounds screened for in vitro activity against epimastigotes and trypomastigotes of Trypanosoma cruzi and promastigotes of Leishmania amazonensis as well as mammalian toxicity on LLCMK2 cells and J774 macrophages, analogues from series 5, 6, 7, 9, 12, and 13 displayed high activity at micromolar IC50 and EC50 concentrations. Sixteen quinoxaline derivatives were selected and evaluated on T. cruzi and/or L. amazonensis amastigotes. The most active compounds were 6a-b and 7d-e, on all evolutive forms of L. amazonensis and T. cruzi evaluated with IC50 values 0.1–0.8 μM on promastigotes and epimastigotes 1.4–8.6 on amastigotes. Compounds 5k, 12b and 13a were the most selective (SI = 19.5–38.4) on amastigotes of T. cruzi. In general their activity was directly related to the methylsulfoxyl, methylsulfonyl, and amine groups as well as the presence of chorine or bromine in the molecules. The current results indicate that these quinoxaline derivatives are novel and promising agents for further development towards a treatment for Chagas’ disease and leishmaniasis.
科研通智能强力驱动
Strongly Powered by AbleSci AI