Kola A. Oluwafemi, Oluwatoba E. Oyeneyin, Damilare D. Babatunde, Eric B. Agbaffa, Jane A. Aigbogun, Oluwakayode O. Odeja, Abiodun V. Emmanuel
{"title":"寄生原生动物：探索N，N'-双[2-（5-溴-7-氮杂苯并咪唑-1-基）-2-氧乙基]乙烯-1,3-二胺及其环己基-1,2-二胺类似物作为TryR和Pf-DHODH抑制剂的潜力。","authors":"Kola A. Oluwafemi, Oluwatoba E. Oyeneyin, Damilare D. Babatunde, Eric B. Agbaffa, Jane A. Aigbogun, Oluwakayode O. Odeja, Abiodun V. Emmanuel","doi":"10.1007/s11686-023-00719-5","DOIUrl":null,"url":null,"abstract":"<div><h3>Purpose</h3><p>Major human parasitic protozoans, such as <i>Plasmodium falciparum</i> and <i>Trypanosoma brucei</i>, cause malaria and trypanosomiasis also known as sleeping sickness. In anti-parasitic drug discovery research, <i>trypanothione reductase</i> (TryR) <i>and P. falciparum dihydroorotate dehydrogenase</i> (<i>Pf-</i>DHODH) enzymes are key drug targets in <i>T. brucei</i> and <i>P. falciparum</i>, respectively. The possibility of co-infection of single host by <i>T. brucei</i> and <i>P. falciparum</i> is because both parasites exist in sub-Saharan Africa and the problem of parasite drug resistance necessitates the discovery of new scaffolds, which are strange to the organisms causing these infectious diseases—new scaffolds may help overcome established resistance mechanisms of the organisms.</p><h3>Method</h3><p>In this study, <i>N,N’</i>-bis[<i>2</i>-(<i>5</i>-bromo-<i>7</i>-azabenzimidazol-1-yl)-<i>2</i>-oxoethyl]ethylene-<i>1,3</i>-diamine and its cyclohexyl-<i>1,2</i>-diamine analogue were explored for their inhibitory potential against TryR and <i>Pf-</i>DHODH by engaging density functional study, molecular dynamic simulations, drug-likeness, in silico and <i>in vitro</i> studies</p><h3>Results/Conclusion</h3><p>Results obtained indicated excellent binding potential of the ligands to the receptors and good ADMET (adsorption, desorption, metabolism, excretion, and toxicity) properties.</p><h3>Graphical Abstract</h3>\n<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6932,"journal":{"name":"Acta Parasitologica","volume":"68 4","pages":"807 - 819"},"PeriodicalIF":1.2000,"publicationDate":"2023-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Parasitic Protozoans: Exploring the Potential of N,N’-Bis[2-(5-bromo-7-azabenzimidazol-1-yl)-2-oxoethyl]ethylene-1,3-Diamine and Its Cyclohexyl-1,2-diamine Analogue as TryR and Pf-DHODH Inhibitors\",\"authors\":\"Kola A. 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The possibility of co-infection of single host by <i>T. brucei</i> and <i>P. falciparum</i> is because both parasites exist in sub-Saharan Africa and the problem of parasite drug resistance necessitates the discovery of new scaffolds, which are strange to the organisms causing these infectious diseases—new scaffolds may help overcome established resistance mechanisms of the organisms.</p><h3>Method</h3><p>In this study, <i>N,N’</i>-bis[<i>2</i>-(<i>5</i>-bromo-<i>7</i>-azabenzimidazol-1-yl)-<i>2</i>-oxoethyl]ethylene-<i>1,3</i>-diamine and its cyclohexyl-<i>1,2</i>-diamine analogue were explored for their inhibitory potential against TryR and <i>Pf-</i>DHODH by engaging density functional study, molecular dynamic simulations, drug-likeness, in silico and <i>in vitro</i> studies</p><h3>Results/Conclusion</h3><p>Results obtained indicated excellent binding potential of the ligands to the receptors and good ADMET (adsorption, desorption, metabolism, excretion, and toxicity) properties.</p><h3>Graphical Abstract</h3>\\n<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>\",\"PeriodicalId\":6932,\"journal\":{\"name\":\"Acta Parasitologica\",\"volume\":\"68 4\",\"pages\":\"807 - 819\"},\"PeriodicalIF\":1.2000,\"publicationDate\":\"2023-10-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Acta Parasitologica\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://link.springer.com/article/10.1007/s11686-023-00719-5\",\"RegionNum\":3,\"RegionCategory\":\"农林科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"PARASITOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta Parasitologica","FirstCategoryId":"3","ListUrlMain":"https://link.springer.com/article/10.1007/s11686-023-00719-5","RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"PARASITOLOGY","Score":null,"Total":0}
Parasitic Protozoans: Exploring the Potential of N,N’-Bis[2-(5-bromo-7-azabenzimidazol-1-yl)-2-oxoethyl]ethylene-1,3-Diamine and Its Cyclohexyl-1,2-diamine Analogue as TryR and Pf-DHODH Inhibitors
Purpose
Major human parasitic protozoans, such as Plasmodium falciparum and Trypanosoma brucei, cause malaria and trypanosomiasis also known as sleeping sickness. In anti-parasitic drug discovery research, trypanothione reductase (TryR) and P. falciparum dihydroorotate dehydrogenase (Pf-DHODH) enzymes are key drug targets in T. brucei and P. falciparum, respectively. The possibility of co-infection of single host by T. brucei and P. falciparum is because both parasites exist in sub-Saharan Africa and the problem of parasite drug resistance necessitates the discovery of new scaffolds, which are strange to the organisms causing these infectious diseases—new scaffolds may help overcome established resistance mechanisms of the organisms.
Method
In this study, N,N’-bis[2-(5-bromo-7-azabenzimidazol-1-yl)-2-oxoethyl]ethylene-1,3-diamine and its cyclohexyl-1,2-diamine analogue were explored for their inhibitory potential against TryR and Pf-DHODH by engaging density functional study, molecular dynamic simulations, drug-likeness, in silico and in vitro studies
Results/Conclusion
Results obtained indicated excellent binding potential of the ligands to the receptors and good ADMET (adsorption, desorption, metabolism, excretion, and toxicity) properties.
期刊介绍：
Acta Parasitologica is an international journal covering the latest advances in the subject.
Acta Parasitologica publishes original papers on all aspects of parasitology and host-parasite relationships, including the latest discoveries in biochemical and molecular biology of parasites, their physiology, morphology, taxonomy and ecology, as well as original research papers on immunology, pathology, and epidemiology of parasitic diseases in the context of medical, veterinary and biological sciences. The journal also publishes short research notes, invited review articles, book reviews.
The journal was founded in 1953 as "Acta Parasitologica Polonica" by the Polish Parasitological Society and since 1954 has been published by W. Stefanski Institute of Parasitology of the Polish Academy of Sciences in Warsaw. Since 1992 in has appeared as Acta Parasitologica in four issues per year.
![Parasitic Protozoans: Exploring the Potential of N,N’-Bis[2-(5-bromo-7-azabenzimidazol-1-yl)-2-oxoethyl]ethylene-1,3-Diamine and Its Cyclohexyl-1,2-diamine Analogue as TryR and Pf-DHODH Inhibitors](https://img.booksci.cn/booksciimg/2023-10/85252159751726599176.jpg)
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