Vijaykumar D. Nimbarte, Shreya S. Sonak, Sharda A. Ishwarkar, Bharat Rathod, Saiprem Nehlani
{"title":"新型三唑-吲哚衍生物作为有效的可溶性环氧水解酶抑制剂,具有良好的抗癌活性","authors":"Vijaykumar D. Nimbarte, Shreya S. Sonak, Sharda A. Ishwarkar, Bharat Rathod, Saiprem Nehlani","doi":"10.1111/cbdd.70164","DOIUrl":null,"url":null,"abstract":"<div>\n \n <p>A novel series of triazole-linked indole derivatives was designed, synthesized, and evaluated as soluble epoxide hydrolase inhibitors (sEHIs) for their potential anticancer activity. These compounds exhibit strong binding affinity within the hydrophobic pockets of sEH, with compounds 9a and 9b emerging as the most potent inhibitors, achieving IC₅₀ values of 0.270 ± 0.014 nM and 0.358 ± 0.03 nM, respectively, in vitro. In addition, both compounds display significant cytotoxic activity against HeLa cells, with IC₅₀ values of 5.366 ± 0.91 μM and 5.686 ± 0.73 μM, respectively. Molecular docking studies, using the 1ZD5 crystal structure, reveal key hydrogen bond interactions analogous to those observed with 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), providing mechanistic insights into their inhibitory activity. Structure–activity relationship (SAR) analysis further informs the rational optimization of these derivatives for enhanced potency. Overall, these findings highlight triazole-linked indole derivatives as promising lead candidates for the development of sEH-targeted anticancer therapeutics.</p>\n </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"106 3","pages":""},"PeriodicalIF":3.3000,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Novel Triazole-Linked Indole Derivatives as Potent Soluble Epoxy Hydrolase Inhibitors With Promising Anticancer Activity\",\"authors\":\"Vijaykumar D. Nimbarte, Shreya S. Sonak, Sharda A. Ishwarkar, Bharat Rathod, Saiprem Nehlani\",\"doi\":\"10.1111/cbdd.70164\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n <p>A novel series of triazole-linked indole derivatives was designed, synthesized, and evaluated as soluble epoxide hydrolase inhibitors (sEHIs) for their potential anticancer activity. These compounds exhibit strong binding affinity within the hydrophobic pockets of sEH, with compounds 9a and 9b emerging as the most potent inhibitors, achieving IC₅₀ values of 0.270 ± 0.014 nM and 0.358 ± 0.03 nM, respectively, in vitro. In addition, both compounds display significant cytotoxic activity against HeLa cells, with IC₅₀ values of 5.366 ± 0.91 μM and 5.686 ± 0.73 μM, respectively. Molecular docking studies, using the 1ZD5 crystal structure, reveal key hydrogen bond interactions analogous to those observed with 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), providing mechanistic insights into their inhibitory activity. Structure–activity relationship (SAR) analysis further informs the rational optimization of these derivatives for enhanced potency. Overall, these findings highlight triazole-linked indole derivatives as promising lead candidates for the development of sEH-targeted anticancer therapeutics.</p>\\n </div>\",\"PeriodicalId\":143,\"journal\":{\"name\":\"Chemical Biology & Drug Design\",\"volume\":\"106 3\",\"pages\":\"\"},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2025-09-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Chemical Biology & Drug Design\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/cbdd.70164\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Chemical Biology & Drug Design","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/cbdd.70164","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Novel Triazole-Linked Indole Derivatives as Potent Soluble Epoxy Hydrolase Inhibitors With Promising Anticancer Activity
A novel series of triazole-linked indole derivatives was designed, synthesized, and evaluated as soluble epoxide hydrolase inhibitors (sEHIs) for their potential anticancer activity. These compounds exhibit strong binding affinity within the hydrophobic pockets of sEH, with compounds 9a and 9b emerging as the most potent inhibitors, achieving IC₅₀ values of 0.270 ± 0.014 nM and 0.358 ± 0.03 nM, respectively, in vitro. In addition, both compounds display significant cytotoxic activity against HeLa cells, with IC₅₀ values of 5.366 ± 0.91 μM and 5.686 ± 0.73 μM, respectively. Molecular docking studies, using the 1ZD5 crystal structure, reveal key hydrogen bond interactions analogous to those observed with 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), providing mechanistic insights into their inhibitory activity. Structure–activity relationship (SAR) analysis further informs the rational optimization of these derivatives for enhanced potency. Overall, these findings highlight triazole-linked indole derivatives as promising lead candidates for the development of sEH-targeted anticancer therapeutics.
期刊介绍:
Chemical Biology & Drug Design is a peer-reviewed scientific journal that is dedicated to the advancement of innovative science, technology and medicine with a focus on the multidisciplinary fields of chemical biology and drug design. It is the aim of Chemical Biology & Drug Design to capture significant research and drug discovery that highlights new concepts, insight and new findings within the scope of chemical biology and drug design.