用扫描电子和原子力显微镜研究新型强效抗利什曼唑处理大利什曼原虫的超微结构。

Q3 Medicine
Azar Shokri, Mahdi Fakhar, Saeed Emami, Pooria Gill, Javad Akhtari
{"title":"用扫描电子和原子力显微镜研究新型强效抗利什曼唑处理大利什曼原虫的超微结构。","authors":"Azar Shokri,&nbsp;Mahdi Fakhar,&nbsp;Saeed Emami,&nbsp;Pooria Gill,&nbsp;Javad Akhtari","doi":"10.2174/1574891X13666180918121628","DOIUrl":null,"url":null,"abstract":"<p><strong>Aim and background: </strong>Azoles as antifungal drugs have been used to treat leishmaniasis for many years. Several evidences suggesting that the primary target of azoles is the heme protein, which co-catalyzes cytochrome P-450-dependent 14α-demethylation of lanosterol. Little is known about the structural changes caused by azoles with atomic force microscopy (AFM) or scanning electron microscopy (SEM). In the current work, several patented antileishmanial agents reviewed (US8809555) (US 0269803 A1) (TW201802093 A). The present study aimed to determine ultrastructural damage in Leishmania major (L.major) induced by the newly synthesized azole.</p><p><strong>Methods: </strong>In this study, we investigated the morphological alterations of the parasite treated with our new synthesized azole namely trans-2-(4-chlorophenyl)-2,3-dihydro-3-(1Himidazol- 1-yl)-4H-1-benzopyran-4-one (IF-2) against L.major promastigotes stage using two high-resolution microscopic techniques: atomic force microscopy and scanning electron microscopy.</p><p><strong>Results: </strong>The results showed remarkable topographical and morphological alterations in the cell membrane at promastigote stage of L. major treated with the potent investigated azole (IF-2) ( IC50 values ≤8.9 µg/mL). Both techniques revealed membrane damage and also losing the flagellum in the observed cells.</p><p><strong>Conclusion: </strong>Our results strongly confirm the Leishmania cell wall as a potent target for the new synthesized azole (IF-2). Accordingly, focus on membrane integrity and glycoconjugates of Leishmania parasite to design new therapeutic agents is recommended.</p>","PeriodicalId":20909,"journal":{"name":"Recent patents on anti-infective drug discovery","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Ultrastructural Investigation of <i>Leishmania major</i> Promastigotes Treated with A New Potent Antileishmanial Azole Using Scanning Electron and Atomic Force Microscopes.\",\"authors\":\"Azar Shokri,&nbsp;Mahdi Fakhar,&nbsp;Saeed Emami,&nbsp;Pooria Gill,&nbsp;Javad Akhtari\",\"doi\":\"10.2174/1574891X13666180918121628\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Aim and background: </strong>Azoles as antifungal drugs have been used to treat leishmaniasis for many years. Several evidences suggesting that the primary target of azoles is the heme protein, which co-catalyzes cytochrome P-450-dependent 14α-demethylation of lanosterol. Little is known about the structural changes caused by azoles with atomic force microscopy (AFM) or scanning electron microscopy (SEM). In the current work, several patented antileishmanial agents reviewed (US8809555) (US 0269803 A1) (TW201802093 A). The present study aimed to determine ultrastructural damage in Leishmania major (L.major) induced by the newly synthesized azole.</p><p><strong>Methods: </strong>In this study, we investigated the morphological alterations of the parasite treated with our new synthesized azole namely trans-2-(4-chlorophenyl)-2,3-dihydro-3-(1Himidazol- 1-yl)-4H-1-benzopyran-4-one (IF-2) against L.major promastigotes stage using two high-resolution microscopic techniques: atomic force microscopy and scanning electron microscopy.</p><p><strong>Results: </strong>The results showed remarkable topographical and morphological alterations in the cell membrane at promastigote stage of L. major treated with the potent investigated azole (IF-2) ( IC50 values ≤8.9 µg/mL). Both techniques revealed membrane damage and also losing the flagellum in the observed cells.</p><p><strong>Conclusion: </strong>Our results strongly confirm the Leishmania cell wall as a potent target for the new synthesized azole (IF-2). Accordingly, focus on membrane integrity and glycoconjugates of Leishmania parasite to design new therapeutic agents is recommended.</p>\",\"PeriodicalId\":20909,\"journal\":{\"name\":\"Recent patents on anti-infective drug discovery\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2018-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Recent patents on anti-infective drug discovery\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.2174/1574891X13666180918121628\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Recent patents on anti-infective drug discovery","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2174/1574891X13666180918121628","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 0

摘要

目的与背景:唑类药物作为抗真菌药物用于治疗利什曼病已有多年历史。一些证据表明,唑类药物的主要靶点是血红素蛋白,该蛋白协同催化细胞色素p -450依赖性的羊毛甾醇的14α-去甲基化。原子力显微镜(AFM)和扫描电子显微镜(SEM)对偶氮引起的结构变化知之甚少。本研究综述了几种专利抗利什曼原虫药物(US8809555) (US 0269803 A1) (TW201802093 A),旨在确定新合成的唑对利什曼原虫(L.major)的超微结构损伤。方法:采用原子力显微镜和扫描电镜两种高分辨率显微技术,研究了新合成的反式-2-(4-氯苯基)-2,3-二氢-3-(1 -咪唑-1-基)- 4h -1-苯并吡喃-4-酮(IF-2)对L.major promastigotes期寄生虫的形态学改变。结果:所研究的强效唑(IF-2)处理后,L. major的细胞膜出现了显著的地形和形态变化(IC50值≤8.9µg/mL)。两种技术都显示了所观察细胞的膜损伤和鞭毛的丢失。结论:利什曼原虫细胞壁是新合成的唑(IF-2)的有效靶点。因此,建议从利什曼原虫的膜完整性和糖缀合物的角度设计新的治疗药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Ultrastructural Investigation of Leishmania major Promastigotes Treated with A New Potent Antileishmanial Azole Using Scanning Electron and Atomic Force Microscopes.

Aim and background: Azoles as antifungal drugs have been used to treat leishmaniasis for many years. Several evidences suggesting that the primary target of azoles is the heme protein, which co-catalyzes cytochrome P-450-dependent 14α-demethylation of lanosterol. Little is known about the structural changes caused by azoles with atomic force microscopy (AFM) or scanning electron microscopy (SEM). In the current work, several patented antileishmanial agents reviewed (US8809555) (US 0269803 A1) (TW201802093 A). The present study aimed to determine ultrastructural damage in Leishmania major (L.major) induced by the newly synthesized azole.

Methods: In this study, we investigated the morphological alterations of the parasite treated with our new synthesized azole namely trans-2-(4-chlorophenyl)-2,3-dihydro-3-(1Himidazol- 1-yl)-4H-1-benzopyran-4-one (IF-2) against L.major promastigotes stage using two high-resolution microscopic techniques: atomic force microscopy and scanning electron microscopy.

Results: The results showed remarkable topographical and morphological alterations in the cell membrane at promastigote stage of L. major treated with the potent investigated azole (IF-2) ( IC50 values ≤8.9 µg/mL). Both techniques revealed membrane damage and also losing the flagellum in the observed cells.

Conclusion: Our results strongly confirm the Leishmania cell wall as a potent target for the new synthesized azole (IF-2). Accordingly, focus on membrane integrity and glycoconjugates of Leishmania parasite to design new therapeutic agents is recommended.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Recent patents on anti-infective drug discovery
Recent patents on anti-infective drug discovery Medicine-Pharmacology (medical)
CiteScore
2.40
自引率
0.00%
发文量
1
期刊介绍: Recent Patents on Anti-Infective Drug Discovery publishes review articles on recent patents in the field of anti-infective drug discovery e.g. novel bioactive compounds, analogs & targets. A selection of important and recent patents on anti-infective drug discovery is also included in the journal. The journal is essential reading for all researchers involved in anti-infective drug design and discovery.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信