开发抗幽门螺杆菌感染的临床前候选药物的研究。

IF 3.8 2区 医学 Q2 CHEMISTRY, MEDICINAL
Haritha Dilip, Deepika Khasa, Ramya V K, Parvinder Kaur, Siva Shanmugam, Naveenkumar Chakenalli, Radhakrishanan Shandil, Shridhar Narayanan, Vijay Thiruvenkatam, Sivapriya Kirubakaran
{"title":"开发抗幽门螺杆菌感染的临床前候选药物的研究。","authors":"Haritha Dilip, Deepika Khasa, Ramya V K, Parvinder Kaur, Siva Shanmugam, Naveenkumar Chakenalli, Radhakrishanan Shandil, Shridhar Narayanan, Vijay Thiruvenkatam, Sivapriya Kirubakaran","doi":"10.1021/acsinfecdis.5c00383","DOIUrl":null,"url":null,"abstract":"<p><p><i>Helicobacter pylori</i> (<i>H. pylori</i>) infection, a precursor to gastritis and gastric cancer, is one of the many infectious diseases that pose a challenge to the progress of developing nations. The present study is the first report on the development of a set of benzopyridine-fused benzimidazoles, leading to the identification of a lead and its further optimization as a potential preclinical candidate for treating <i>H. pylori</i> infection. The designed synthetic method for these derivatives is devoid of toxic chemicals and sophisticated reaction setups, using economical and readily available chemicals to produce benzopyridine-fused (namely, quinoline/isoquinoline-fused) benzimidazole derivatives in moderate-to-good yields. These small molecules showed promising <i>H. pylori</i> growth inhibition, and a lead molecule was identified and evaluated for its antibacterial potential. Following the promising results of the growth inhibition displayed by this series of inhibitors, lead optimization studies were carried out on the best inhibitor of <i>H. pylori</i> growth, highlighting the possibility of developing this core molecule for preclinical trials.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":3.8000,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Studies on Developing a Preclinical Candidate to Fight <i>Helicobacter Pylori</i> Infection.\",\"authors\":\"Haritha Dilip, Deepika Khasa, Ramya V K, Parvinder Kaur, Siva Shanmugam, Naveenkumar Chakenalli, Radhakrishanan Shandil, Shridhar Narayanan, Vijay Thiruvenkatam, Sivapriya Kirubakaran\",\"doi\":\"10.1021/acsinfecdis.5c00383\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p><i>Helicobacter pylori</i> (<i>H. pylori</i>) infection, a precursor to gastritis and gastric cancer, is one of the many infectious diseases that pose a challenge to the progress of developing nations. The present study is the first report on the development of a set of benzopyridine-fused benzimidazoles, leading to the identification of a lead and its further optimization as a potential preclinical candidate for treating <i>H. pylori</i> infection. The designed synthetic method for these derivatives is devoid of toxic chemicals and sophisticated reaction setups, using economical and readily available chemicals to produce benzopyridine-fused (namely, quinoline/isoquinoline-fused) benzimidazole derivatives in moderate-to-good yields. These small molecules showed promising <i>H. pylori</i> growth inhibition, and a lead molecule was identified and evaluated for its antibacterial potential. Following the promising results of the growth inhibition displayed by this series of inhibitors, lead optimization studies were carried out on the best inhibitor of <i>H. pylori</i> growth, highlighting the possibility of developing this core molecule for preclinical trials.</p>\",\"PeriodicalId\":17,\"journal\":{\"name\":\"ACS Infectious Diseases\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.8000,\"publicationDate\":\"2025-07-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ACS Infectious Diseases\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1021/acsinfecdis.5c00383\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Infectious Diseases","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1021/acsinfecdis.5c00383","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0

摘要

幽门螺杆菌(h.p ylori)感染是胃炎和胃癌的前兆,是对发展中国家的进步构成挑战的众多传染病之一。本研究首次报道了一组苯并吡啶融合苯并咪唑的发展,从而确定了一种铅并进一步优化其作为治疗幽门螺杆菌感染的潜在临床前候选药物。所设计的这些衍生物的合成方法不含有毒化学品和复杂的反应装置,使用经济和容易获得的化学品以中等至较高的收率生产苯并吡啶-融合(即喹啉/异喹啉-融合)苯并咪唑衍生物。这些小分子对幽门螺杆菌生长有抑制作用,并鉴定了一个铅分子,并对其抗菌潜力进行了评价。在这一系列抑制剂显示出良好的生长抑制效果之后,对幽门螺杆菌生长的最佳抑制剂进行了先导优化研究,突出了开发该核心分子用于临床前试验的可能性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Studies on Developing a Preclinical Candidate to Fight Helicobacter Pylori Infection.

Helicobacter pylori (H. pylori) infection, a precursor to gastritis and gastric cancer, is one of the many infectious diseases that pose a challenge to the progress of developing nations. The present study is the first report on the development of a set of benzopyridine-fused benzimidazoles, leading to the identification of a lead and its further optimization as a potential preclinical candidate for treating H. pylori infection. The designed synthetic method for these derivatives is devoid of toxic chemicals and sophisticated reaction setups, using economical and readily available chemicals to produce benzopyridine-fused (namely, quinoline/isoquinoline-fused) benzimidazole derivatives in moderate-to-good yields. These small molecules showed promising H. pylori growth inhibition, and a lead molecule was identified and evaluated for its antibacterial potential. Following the promising results of the growth inhibition displayed by this series of inhibitors, lead optimization studies were carried out on the best inhibitor of H. pylori growth, highlighting the possibility of developing this core molecule for preclinical trials.

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
ACS Infectious Diseases
ACS Infectious Diseases CHEMISTRY, MEDICINALINFECTIOUS DISEASES&nb-INFECTIOUS DISEASES
CiteScore
9.70
自引率
3.80%
发文量
213
期刊介绍: ACS Infectious Diseases will be the first journal to highlight chemistry and its role in this multidisciplinary and collaborative research area. The journal will cover a diverse array of topics including, but not limited to: * Discovery and development of new antimicrobial agents — identified through target- or phenotypic-based approaches as well as compounds that induce synergy with antimicrobials. * Characterization and validation of drug target or pathways — use of single target and genome-wide knockdown and knockouts, biochemical studies, structural biology, new technologies to facilitate characterization and prioritization of potential drug targets. * Mechanism of drug resistance — fundamental research that advances our understanding of resistance; strategies to prevent resistance. * Mechanisms of action — use of genetic, metabolomic, and activity- and affinity-based protein profiling to elucidate the mechanism of action of clinical and experimental antimicrobial agents. * Host-pathogen interactions — tools for studying host-pathogen interactions, cellular biochemistry of hosts and pathogens, and molecular interactions of pathogens with host microbiota. * Small molecule vaccine adjuvants for infectious disease. * Viral and bacterial biochemistry and molecular biology.
×
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:604180095
Book学术官方微信