新型基于3-硝基三唑的酰胺和甲醇作为双功能抗恰加斯病药物。
Novel 3-nitrotriazole-based amides and carbinols as bifunctional antichagasic agents.
作者信息
Papadopoulou Maria V, Bloomer William D, Lepesheva Galina I, Rosenzweig Howard S, Kaiser Marcel, Aguilera-Venegas Benjamín, Wilkinson Shane R, Chatelain Eric, Ioset Jean-Robert
机构信息
NorthShore University HealthSystem , Evanston, Illinois 60201, United States.
出版信息
J Med Chem. 2015 Feb 12;58(3):1307-19. doi: 10.1021/jm5015742. Epub 2015 Jan 23.
Abstract
3-Nitro-1H-1,2,4-triazole-based amides with a linear, rigid core and 3-nitrotriazole-based fluconazole analogues were synthesized as dual functioning antitrypanosomal agents. Such compounds are excellent substrates for type I nitroreductase (NTR) located in the mitochondrion of trypanosomatids and, at the same time, act as inhibitors of the sterol 14α-demethylase (T. cruzi CYP51) enzyme. Because combination treatments against parasites are often superior to monotherapy, we believe that this emerging class of bifunctional compounds may introduce a new generation of antitrypanosomal drugs. In the present work, the synthesis and in vitro and in vivo evaluation of such compounds is discussed.
摘要
合成了具有线性、刚性核心的基于3-硝基-1H-1,2,4-三唑的酰胺以及基于3-硝基三唑的氟康唑类似物作为双功能抗锥虫剂。这类化合物是锥虫线粒体中I型硝基还原酶（NTR）的优良底物，同时还可作为甾醇14α-脱甲基酶（克氏锥虫CYP51）的抑制剂。由于针对寄生虫的联合治疗通常优于单一疗法，我们认为这类新兴的双功能化合物可能会带来新一代抗锥虫药物。在本研究中，讨论了这类化合物的合成及其体外和体内评价。
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