新的单纯型1型溶性感染吡啶体系衍生物作为抗疱疹的新靶点

M. Costa, Viveca A Giongo, C. Cirne-Santos, Caroline Barros, Valéria Garrido, T. M. Souza, J. L. Abrantes, Luiz C. S. Pinheiro, Sergio Pinheiro, A. Bernardino, I. Paixão
{"title":"新的单纯型1型溶性感染吡啶体系衍生物作为抗疱疹的新靶点","authors":"M. Costa, Viveca A Giongo, C. Cirne-Santos, Caroline Barros, Valéria Garrido, T. M. Souza, J. L. Abrantes, Luiz C. S. Pinheiro, Sergio Pinheiro, A. Bernardino, I. Paixão","doi":"10.7439/IJPR.V7I7.3932","DOIUrl":null,"url":null,"abstract":"The pyridine system derivatives have been studied as antiviral drug new models against HIV infection using bioisosterism as a powerful tool. In the last decades, the number of this work, thienopyridine derivatives were evaluated as an HSV-1 inhibitor to since the elevated number of acyclovir resistance in immunocompromised patients could promote a continuous viral pool increase and disease recurrence. In these substances, thienopyridine derivative with radical nitrate in para position (109) was able to inhibit 99% of HSV-1 replication in Vero cells with EC 50 value of 100 pM, and SI value three times higher than acyclovir. In kinetic enzymatic assay this substance was also able to inhibit about 50% of HSV-1 DNA polymerase but in a non-competitive mechanism a new synergic system to control herpes infections. Preliminary in vivo model studies revealed that substance 109 is toxic when administered in 300 g/mL concentrations. In this work, we concluded that thienopyridine derivatives can be considered a promising new anti-HSV-1 drug and can be used for clinical testing.","PeriodicalId":14194,"journal":{"name":"International Journal of Pharmacological Research","volume":"43 1","pages":"148-153"},"PeriodicalIF":0.0000,"publicationDate":"2017-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"New simplex Type 1 lytic infection pyridine system derivative as a novel goal against Herpes\",\"authors\":\"M. Costa, Viveca A Giongo, C. Cirne-Santos, Caroline Barros, Valéria Garrido, T. M. Souza, J. L. Abrantes, Luiz C. S. Pinheiro, Sergio Pinheiro, A. Bernardino, I. Paixão\",\"doi\":\"10.7439/IJPR.V7I7.3932\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"The pyridine system derivatives have been studied as antiviral drug new models against HIV infection using bioisosterism as a powerful tool. In the last decades, the number of this work, thienopyridine derivatives were evaluated as an HSV-1 inhibitor to since the elevated number of acyclovir resistance in immunocompromised patients could promote a continuous viral pool increase and disease recurrence. In these substances, thienopyridine derivative with radical nitrate in para position (109) was able to inhibit 99% of HSV-1 replication in Vero cells with EC 50 value of 100 pM, and SI value three times higher than acyclovir. In kinetic enzymatic assay this substance was also able to inhibit about 50% of HSV-1 DNA polymerase but in a non-competitive mechanism a new synergic system to control herpes infections. Preliminary in vivo model studies revealed that substance 109 is toxic when administered in 300 g/mL concentrations. In this work, we concluded that thienopyridine derivatives can be considered a promising new anti-HSV-1 drug and can be used for clinical testing.\",\"PeriodicalId\":14194,\"journal\":{\"name\":\"International Journal of Pharmacological Research\",\"volume\":\"43 1\",\"pages\":\"148-153\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2017-07-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Pharmacological Research\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.7439/IJPR.V7I7.3932\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Pharmacological Research","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.7439/IJPR.V7I7.3932","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

摘要

利用生物同位体作为一种强有力的工具,吡啶系衍生物已被研究为抗病毒药物的新模型。在过去的几十年里,这项工作的数量,噻吩吡啶衍生物被评估为HSV-1抑制剂,因为免疫功能低下患者中阿昔洛韦耐药数量的增加可以促进病毒池的持续增加和疾病复发。在这些物质中,噻吩吡啶衍生物的对位硝酸盐自由基(109)能够抑制99%的HSV-1在Vero细胞中的复制,EC 50值为100 pM, SI值比阿昔洛韦高3倍。在动力学酶分析中,该物质也能够抑制约50%的HSV-1 DNA聚合酶,但在非竞争性机制中,一个新的协同系统来控制疱疹感染。初步体内模型研究表明,物质109以300 g/mL的浓度施用时是有毒的。本研究认为噻吩吡啶衍生物是一种很有前景的抗hsv -1新药,可用于临床试验。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
New simplex Type 1 lytic infection pyridine system derivative as a novel goal against Herpes
The pyridine system derivatives have been studied as antiviral drug new models against HIV infection using bioisosterism as a powerful tool. In the last decades, the number of this work, thienopyridine derivatives were evaluated as an HSV-1 inhibitor to since the elevated number of acyclovir resistance in immunocompromised patients could promote a continuous viral pool increase and disease recurrence. In these substances, thienopyridine derivative with radical nitrate in para position (109) was able to inhibit 99% of HSV-1 replication in Vero cells with EC 50 value of 100 pM, and SI value three times higher than acyclovir. In kinetic enzymatic assay this substance was also able to inhibit about 50% of HSV-1 DNA polymerase but in a non-competitive mechanism a new synergic system to control herpes infections. Preliminary in vivo model studies revealed that substance 109 is toxic when administered in 300 g/mL concentrations. In this work, we concluded that thienopyridine derivatives can be considered a promising new anti-HSV-1 drug and can be used for clinical testing.
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
自引率
0.00%
发文量
0
×
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