Alonzo González-González, Oscar Sánchez-Sánchez, Lilián Yépez-Mulia, Timoteo Delgado-Maldonado, Lenci K Vázquez-Jiménez, Gabriel López-Velázquez, José Ignacio de la Mora-de la Mora, Sebastian Pacheco-Gutierrez, Laura Chino-Ríos, Diego Arias, Adriana Moreno-Rodríguez, Alma Paz-González, Eyra Ortíz-Pérez, Gildardo Rivera
{"title":"拓展喹喔啉-1,4-二-N-氧化物正丁酯和异丁酯衍生物对蓝氏贾第鞭毛虫、阴道毛滴虫和组织溶解恩塔莫阿巴的抗原虫活性和作用机制。体外和硅学方法。","authors":"Alonzo González-González, Oscar Sánchez-Sánchez, Lilián Yépez-Mulia, Timoteo Delgado-Maldonado, Lenci K Vázquez-Jiménez, Gabriel López-Velázquez, José Ignacio de la Mora-de la Mora, Sebastian Pacheco-Gutierrez, Laura Chino-Ríos, Diego Arias, Adriana Moreno-Rodríguez, Alma Paz-González, Eyra Ortíz-Pérez, Gildardo Rivera","doi":"10.1080/14756366.2024.2413018","DOIUrl":null,"url":null,"abstract":"<p><p>In this study, n-butyl and iso-butyl quinoxaline-7-carboxylate-1,4-di-<i>N</i>-oxide derivatives were evaluated <i>in vitro</i> against <i>Giardia lamblia</i> (<i>G. lamblia</i>)<i>, Trichomonas vaginalis</i> (<i>T. vaginalis</i>), and <i>Entamoeba histolytica</i> (<i>E. histolytica</i>). The potential mechanism of action determination was approached by <i>in silico</i> analysis on <i>G. lamblia</i> and <i>T. vaginalis</i> triosephosphate isomerase (<i>Gl</i>TIM and <i>Tv</i>TIM, respectively), and on <i>E. histolytica</i> thioredoxin reductase (<i>EhTrxR</i>). Enzyme inactivation assays were performed on recombinant G<i>l</i>TIM and <i>Eh</i>TrxR. Compound T-167 showed the best giardicidal activity (IC<sub>50</sub> = 25.53 nM) and the highest inactivation efficiency against G<i>l</i>TIM without significantly perturbing its human homolog. Compounds T-142 and T-143 showed the best amoebicidal (IC<sub>50</sub> = 9.20 nM) and trichomonacidal (IC<sub>50</sub> = 45.20 nM) activity, respectively. Additionally, T-143 had a high activity as giardicial (IC<sub>50</sub> = 29.13 nM) and amoebicidal (IC<sub>50</sub> = 15.14 nM), proposing it as a broad-spectrum antiparasitic agent. Compounds T-145, and T-161 were the best <i>Eh</i>TrxR inhibitors with IC<sub>50</sub> of 16 µM, and 18 µM, respectively.</p>","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"39 1","pages":"2413018"},"PeriodicalIF":5.6000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11523249/pdf/","citationCount":"0","resultStr":"{\"title\":\"Expanding the antiprotozoal activity and the mechanism of action of n-butyl and iso-butyl ester of quinoxaline-1,4-di-<i>N</i>-oxide derivatives against <i>Giardia lamblia</i>, <i>Trichomonas vaginalis</i>, and <i>Entamoeba histolytica.</i> An <i>in vitro</i> and <i>in silico</i> approach.\",\"authors\":\"Alonzo González-González, Oscar Sánchez-Sánchez, Lilián Yépez-Mulia, Timoteo Delgado-Maldonado, Lenci K Vázquez-Jiménez, Gabriel López-Velázquez, José Ignacio de la Mora-de la Mora, Sebastian Pacheco-Gutierrez, Laura Chino-Ríos, Diego Arias, Adriana Moreno-Rodríguez, Alma Paz-González, Eyra Ortíz-Pérez, Gildardo Rivera\",\"doi\":\"10.1080/14756366.2024.2413018\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>In this study, n-butyl and iso-butyl quinoxaline-7-carboxylate-1,4-di-<i>N</i>-oxide derivatives were evaluated <i>in vitro</i> against <i>Giardia lamblia</i> (<i>G. lamblia</i>)<i>, Trichomonas vaginalis</i> (<i>T. vaginalis</i>), and <i>Entamoeba histolytica</i> (<i>E. histolytica</i>). The potential mechanism of action determination was approached by <i>in silico</i> analysis on <i>G. lamblia</i> and <i>T. vaginalis</i> triosephosphate isomerase (<i>Gl</i>TIM and <i>Tv</i>TIM, respectively), and on <i>E. histolytica</i> thioredoxin reductase (<i>EhTrxR</i>). Enzyme inactivation assays were performed on recombinant G<i>l</i>TIM and <i>Eh</i>TrxR. Compound T-167 showed the best giardicidal activity (IC<sub>50</sub> = 25.53 nM) and the highest inactivation efficiency against G<i>l</i>TIM without significantly perturbing its human homolog. Compounds T-142 and T-143 showed the best amoebicidal (IC<sub>50</sub> = 9.20 nM) and trichomonacidal (IC<sub>50</sub> = 45.20 nM) activity, respectively. Additionally, T-143 had a high activity as giardicial (IC<sub>50</sub> = 29.13 nM) and amoebicidal (IC<sub>50</sub> = 15.14 nM), proposing it as a broad-spectrum antiparasitic agent. Compounds T-145, and T-161 were the best <i>Eh</i>TrxR inhibitors with IC<sub>50</sub> of 16 µM, and 18 µM, respectively.</p>\",\"PeriodicalId\":15769,\"journal\":{\"name\":\"Journal of Enzyme Inhibition and Medicinal Chemistry\",\"volume\":\"39 1\",\"pages\":\"2413018\"},\"PeriodicalIF\":5.6000,\"publicationDate\":\"2024-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11523249/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Enzyme Inhibition and Medicinal Chemistry\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/14756366.2024.2413018\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/10/29 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Enzyme Inhibition and Medicinal Chemistry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/14756366.2024.2413018","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/10/29 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Expanding the antiprotozoal activity and the mechanism of action of n-butyl and iso-butyl ester of quinoxaline-1,4-di-N-oxide derivatives against Giardia lamblia, Trichomonas vaginalis, and Entamoeba histolytica. An in vitro and in silico approach.
In this study, n-butyl and iso-butyl quinoxaline-7-carboxylate-1,4-di-N-oxide derivatives were evaluated in vitro against Giardia lamblia (G. lamblia), Trichomonas vaginalis (T. vaginalis), and Entamoeba histolytica (E. histolytica). The potential mechanism of action determination was approached by in silico analysis on G. lamblia and T. vaginalis triosephosphate isomerase (GlTIM and TvTIM, respectively), and on E. histolytica thioredoxin reductase (EhTrxR). Enzyme inactivation assays were performed on recombinant GlTIM and EhTrxR. Compound T-167 showed the best giardicidal activity (IC50 = 25.53 nM) and the highest inactivation efficiency against GlTIM without significantly perturbing its human homolog. Compounds T-142 and T-143 showed the best amoebicidal (IC50 = 9.20 nM) and trichomonacidal (IC50 = 45.20 nM) activity, respectively. Additionally, T-143 had a high activity as giardicial (IC50 = 29.13 nM) and amoebicidal (IC50 = 15.14 nM), proposing it as a broad-spectrum antiparasitic agent. Compounds T-145, and T-161 were the best EhTrxR inhibitors with IC50 of 16 µM, and 18 µM, respectively.
期刊介绍:
Journal of Enzyme Inhibition and Medicinal Chemistry publishes open access research on enzyme inhibitors, inhibitory processes, and agonist/antagonist receptor interactions in the development of medicinal and anti-cancer agents.
Journal of Enzyme Inhibition and Medicinal Chemistry aims to provide an international and interdisciplinary platform for the latest findings in enzyme inhibition research.
The journal’s focus includes current developments in:
Enzymology;
Cell biology;
Chemical biology;
Microbiology;
Physiology;
Pharmacology leading to drug design;
Molecular recognition processes;
Distribution and metabolism of biologically active compounds.