Anna Seetsi , David D. N'Da , Nthatisi Nyembe , Keisuke Suganuma , Tsepo Ramatla , Oriel Thekisoe
{"title":"合成的硝基呋喃妥因-三唑混合物对引起动物非洲锥虫病的锥虫的体外抗锥虫活性。","authors":"Anna Seetsi , David D. N'Da , Nthatisi Nyembe , Keisuke Suganuma , Tsepo Ramatla , Oriel Thekisoe","doi":"10.1016/j.exppara.2024.108711","DOIUrl":null,"url":null,"abstract":"<div><p>Animal African trypanosomosis (AAT) is a disease caused by <em>Trypanosoma brucei brucei</em>, <em>T. vivax</em>, <em>T. evansi</em> and <em>T. congolense</em> which are mainly transmitted by tsetse flies (maybe the family/genus scientific name for the tsetse flies here?). Synthetic trypanocidal drugs are used to control AAT but have reduced efficacy due to emergence of drug resistant trypanosomes. Therefore, there is a need for the continued development of new safe and effective drugs. The aim of this study was to evaluate the <em>in vitro</em> anti-trypanosomal activity of novel nitrofurantoin compounds against trypanosomes (<em>Trypanosoma brucei brucei</em>, <em>T. evansi</em> and <em>T. congolense</em>) causing AAT. This study assessed previously synthesized nineteen nitrofurantoin-triazole (NFT-TZ) hybrids against animal trypanosomes and evaluated their cytotoxicity using Madin–Darby bovine kidney cells. The <em>n-</em>alkyl sub-series hybrids, <strong>8</strong> (IC<sub>50</sub> 0.09 ± 0.02 μM; SI 686.45) and <strong>9</strong> (IC<sub>50</sub> 0.07 ± 0.04 μM; SI 849.31) had the highest anti-trypanosomal activity against <em>T. b. brucei</em>. On the contrary, the nonyl <strong>6</strong> (IC<sub>50</sub> 0.12 ± 0.06 μM; SI 504.57) and nitrobenzyl <strong>18</strong> (IC<sub>50</sub> 0.11 ± 0.03 μM; SI 211.07) displayed the highest trypanocidal activity against <em>T. evansi</em>. The nonyl hybrid <strong>6</strong> (IC<sub>50</sub> 0.02 ± 0.01 μM<strong>;</strong> SI 6328.76) was also detected alongside the undecyl <strong>8</strong> (IC<sub>50</sub> 0.02 ± 0.01 μM; SI 3454.36) and 3-bromobenzyl <strong>19</strong> (IC<sub>50</sub> 0.02 ± 0.01 μM; SI 2360.41) as the most potent hybrids against <em>T. congolense.</em> These hybrids had weak toxicity effects on the mammalian cells and highly selective submicromolar antiparasitic action efficacy directed towards the trypanosomes, hence they can be regarded as potential trypanocidal leads for further <em>in vivo</em> investigation.</p></div>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":null,"pages":null},"PeriodicalIF":16.4000,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0014489424000146/pdfft?md5=f9c9a4473d114007e998394cba9db9b8&pid=1-s2.0-S0014489424000146-main.pdf","citationCount":"0","resultStr":"{\"title\":\"In vitro antitrypanosomal activity of synthesized nitrofurantoin-triazole hybrids against Trypanosoma species causing animal African trypanosomosis\",\"authors\":\"Anna Seetsi , David D. N'Da , Nthatisi Nyembe , Keisuke Suganuma , Tsepo Ramatla , Oriel Thekisoe\",\"doi\":\"10.1016/j.exppara.2024.108711\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Animal African trypanosomosis (AAT) is a disease caused by <em>Trypanosoma brucei brucei</em>, <em>T. vivax</em>, <em>T. evansi</em> and <em>T. congolense</em> which are mainly transmitted by tsetse flies (maybe the family/genus scientific name for the tsetse flies here?). Synthetic trypanocidal drugs are used to control AAT but have reduced efficacy due to emergence of drug resistant trypanosomes. Therefore, there is a need for the continued development of new safe and effective drugs. The aim of this study was to evaluate the <em>in vitro</em> anti-trypanosomal activity of novel nitrofurantoin compounds against trypanosomes (<em>Trypanosoma brucei brucei</em>, <em>T. evansi</em> and <em>T. congolense</em>) causing AAT. This study assessed previously synthesized nineteen nitrofurantoin-triazole (NFT-TZ) hybrids against animal trypanosomes and evaluated their cytotoxicity using Madin–Darby bovine kidney cells. The <em>n-</em>alkyl sub-series hybrids, <strong>8</strong> (IC<sub>50</sub> 0.09 ± 0.02 μM; SI 686.45) and <strong>9</strong> (IC<sub>50</sub> 0.07 ± 0.04 μM; SI 849.31) had the highest anti-trypanosomal activity against <em>T. b. brucei</em>. On the contrary, the nonyl <strong>6</strong> (IC<sub>50</sub> 0.12 ± 0.06 μM; SI 504.57) and nitrobenzyl <strong>18</strong> (IC<sub>50</sub> 0.11 ± 0.03 μM; SI 211.07) displayed the highest trypanocidal activity against <em>T. evansi</em>. The nonyl hybrid <strong>6</strong> (IC<sub>50</sub> 0.02 ± 0.01 μM<strong>;</strong> SI 6328.76) was also detected alongside the undecyl <strong>8</strong> (IC<sub>50</sub> 0.02 ± 0.01 μM; SI 3454.36) and 3-bromobenzyl <strong>19</strong> (IC<sub>50</sub> 0.02 ± 0.01 μM; SI 2360.41) as the most potent hybrids against <em>T. congolense.</em> These hybrids had weak toxicity effects on the mammalian cells and highly selective submicromolar antiparasitic action efficacy directed towards the trypanosomes, hence they can be regarded as potential trypanocidal leads for further <em>in vivo</em> investigation.</p></div>\",\"PeriodicalId\":1,\"journal\":{\"name\":\"Accounts of Chemical Research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":16.4000,\"publicationDate\":\"2024-02-12\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S0014489424000146/pdfft?md5=f9c9a4473d114007e998394cba9db9b8&pid=1-s2.0-S0014489424000146-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Accounts of Chemical Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0014489424000146\",\"RegionNum\":1,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Accounts of Chemical Research","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0014489424000146","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
In vitro antitrypanosomal activity of synthesized nitrofurantoin-triazole hybrids against Trypanosoma species causing animal African trypanosomosis
Animal African trypanosomosis (AAT) is a disease caused by Trypanosoma brucei brucei, T. vivax, T. evansi and T. congolense which are mainly transmitted by tsetse flies (maybe the family/genus scientific name for the tsetse flies here?). Synthetic trypanocidal drugs are used to control AAT but have reduced efficacy due to emergence of drug resistant trypanosomes. Therefore, there is a need for the continued development of new safe and effective drugs. The aim of this study was to evaluate the in vitro anti-trypanosomal activity of novel nitrofurantoin compounds against trypanosomes (Trypanosoma brucei brucei, T. evansi and T. congolense) causing AAT. This study assessed previously synthesized nineteen nitrofurantoin-triazole (NFT-TZ) hybrids against animal trypanosomes and evaluated their cytotoxicity using Madin–Darby bovine kidney cells. The n-alkyl sub-series hybrids, 8 (IC50 0.09 ± 0.02 μM; SI 686.45) and 9 (IC50 0.07 ± 0.04 μM; SI 849.31) had the highest anti-trypanosomal activity against T. b. brucei. On the contrary, the nonyl 6 (IC50 0.12 ± 0.06 μM; SI 504.57) and nitrobenzyl 18 (IC50 0.11 ± 0.03 μM; SI 211.07) displayed the highest trypanocidal activity against T. evansi. The nonyl hybrid 6 (IC50 0.02 ± 0.01 μM; SI 6328.76) was also detected alongside the undecyl 8 (IC50 0.02 ± 0.01 μM; SI 3454.36) and 3-bromobenzyl 19 (IC50 0.02 ± 0.01 μM; SI 2360.41) as the most potent hybrids against T. congolense. These hybrids had weak toxicity effects on the mammalian cells and highly selective submicromolar antiparasitic action efficacy directed towards the trypanosomes, hence they can be regarded as potential trypanocidal leads for further in vivo investigation.
期刊介绍：
Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance.
Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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