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拓展喹喔啉-1,4-二--氧化物衍生物的正丁基和异丁基酯的抗原生动物活性和作用机制，以对抗 、 和 。一种 和 方法。

Expanding the antiprotozoal activity and the mechanism of action of n-butyl and iso-butyl ester of quinoxaline-1,4-di--oxide derivatives against , , and An and approach.

机构信息

Laboratorio de Biotecnología Farmacéutica, Centro de Biotecnología Genómica, Instituto Politécnico Nacional, Reynosa, México.

Unidad de Investigación Médica en Enfermedades Infecciosas y Parasitarias, Hospital de Pediatría, Instituto Mexicano del Seguro Social, México, México City.

出版信息

J Enzyme Inhib Med Chem. 2024 Dec;39(1):2413018. doi: 10.1080/14756366.2024.2413018. Epub 2024 Oct 29.

DOI:10.1080/14756366.2024.2413018
PMID:39470324
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11523249/
Abstract

In this study, n-butyl and iso-butyl quinoxaline-7-carboxylate-1,4-di--oxide derivatives were evaluated against () (), and (). The potential mechanism of action determination was approached by analysis on and triosephosphate isomerase (TIM and TIM, respectively), and on thioredoxin reductase (). Enzyme inactivation assays were performed on recombinant GTIM and TrxR. Compound T-167 showed the best giardicidal activity (IC = 25.53 nM) and the highest inactivation efficiency against GTIM without significantly perturbing its human homolog. Compounds T-142 and T-143 showed the best amoebicidal (IC = 9.20 nM) and trichomonacidal (IC = 45.20 nM) activity, respectively. Additionally, T-143 had a high activity as giardicial (IC = 29.13 nM) and amoebicidal (IC = 15.14 nM), proposing it as a broad-spectrum antiparasitic agent. Compounds T-145, and T-161 were the best TrxR inhibitors with IC of 16 µM, and 18 µM, respectively.

摘要

在这项研究中，我们评估了正丁基和异丁基喹喔啉-7-羧酸-1,4-二--氧化物衍生物对（）（）、（）和（）的抑制作用。通过对甘油醛-3-磷酸脱氢酶（GTIM）和硫氧还蛋白（TIM 和 TIM）以及硫氧还蛋白还原酶（TrxR）的分析，我们探讨了潜在的作用机制。对重组 GTIM 和 TrxR 进行了酶失活测定。化合物 T-167 表现出最好的杀贾第鞭毛虫活性（IC = 25.53 nM），对 GTIM 的失活效率最高，而对其人类同源物没有明显干扰。化合物 T-142 和 T-143 分别表现出最好的杀阿米巴活性（IC = 9.20 nM）和杀滴虫活性（IC = 45.20 nM）。此外，T-143 对贾第鞭毛虫（IC = 29.13 nM）和阿米巴（IC = 15.14 nM）具有高活性，表明它是一种广谱抗寄生虫药物。化合物 T-145 和 T-161 对 TrxR 的抑制作用最强，IC 分别为 16 μM 和 18 μM。

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