{"title":"磺胺基修饰对塞来昔布的影响：基质金属蛋白酶互作UTX-121衍生物的分子特征。","authors":"Kazuto Ohkura, Atsushi Tabata, Yoshihiro Uto","doi":"10.21873/anticanres.17706","DOIUrl":null,"url":null,"abstract":"<p><strong>Background/aim: </strong>Matrix metalloproteinases (MMPs) are important for extracellular matrix (ECM) degradation with MMP inhibition possibly leading to new antitumor therapies. To examine this possibility, UTX-121, in which the celecoxib sulfonamide was replaced with a methyl ester, was designed to examine the influence of UTX-121 derivatives on MMPs.</p><p><strong>Materials and methods: </strong>HT-1080 cells were incubated with UTX-121 derivatives over 48 h, and antitumor activities (IC<sub>50</sub>) were examined using WST-8 assay. The inhibitory effect of UTX-121 derivatives on MMPs in HT-1080 cells was examined using gelatin zymography. Conformational analyses of UTX-121 derivatives were performed using CAChe-Conflex. The interaction of UTX-121 derivatives with MMPs was analyzed using Molegro Virtual Docker.</p><p><strong>Results: </strong>UTX-121 derivative a2 exhibited enhanced antitumor activity compared to UTX-121. Additionally, derivative a2 demonstrated stronger inhibitory effects on MMP-2, as indicated by reduced band intensity in gelatin zymography, compared to UTX-121. Molecular docking simulations revealed that a2 formed a hydrogen bond with the Tyr<sup>366</sup> residue of MMP-2 <i>via</i> the oxygen atom of its methoxy group, supporting its enhanced interaction and inhibitory potency.</p><p><strong>Conclusion: </strong>UTX-121 derivative a2 showed improved MMP-2 inhibitory activity through specific hydrogen bonding interactions and holds promise as a lead compound for the development of novel MMP-2-targeted anticancer agents.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 8","pages":"3451-3457"},"PeriodicalIF":1.7000,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Effect of Sulfonamide Group Modification on Celecoxib: Molecular Features of Matrix Metalloproteinase Interactive UTX-121 Derivative.\",\"authors\":\"Kazuto Ohkura, Atsushi Tabata, Yoshihiro Uto\",\"doi\":\"10.21873/anticanres.17706\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background/aim: </strong>Matrix metalloproteinases (MMPs) are important for extracellular matrix (ECM) degradation with MMP inhibition possibly leading to new antitumor therapies. To examine this possibility, UTX-121, in which the celecoxib sulfonamide was replaced with a methyl ester, was designed to examine the influence of UTX-121 derivatives on MMPs.</p><p><strong>Materials and methods: </strong>HT-1080 cells were incubated with UTX-121 derivatives over 48 h, and antitumor activities (IC<sub>50</sub>) were examined using WST-8 assay. The inhibitory effect of UTX-121 derivatives on MMPs in HT-1080 cells was examined using gelatin zymography. Conformational analyses of UTX-121 derivatives were performed using CAChe-Conflex. The interaction of UTX-121 derivatives with MMPs was analyzed using Molegro Virtual Docker.</p><p><strong>Results: </strong>UTX-121 derivative a2 exhibited enhanced antitumor activity compared to UTX-121. Additionally, derivative a2 demonstrated stronger inhibitory effects on MMP-2, as indicated by reduced band intensity in gelatin zymography, compared to UTX-121. Molecular docking simulations revealed that a2 formed a hydrogen bond with the Tyr<sup>366</sup> residue of MMP-2 <i>via</i> the oxygen atom of its methoxy group, supporting its enhanced interaction and inhibitory potency.</p><p><strong>Conclusion: </strong>UTX-121 derivative a2 showed improved MMP-2 inhibitory activity through specific hydrogen bonding interactions and holds promise as a lead compound for the development of novel MMP-2-targeted anticancer agents.</p>\",\"PeriodicalId\":8072,\"journal\":{\"name\":\"Anticancer research\",\"volume\":\"45 8\",\"pages\":\"3451-3457\"},\"PeriodicalIF\":1.7000,\"publicationDate\":\"2025-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Anticancer research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.21873/anticanres.17706\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Anticancer research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.21873/anticanres.17706","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"ONCOLOGY","Score":null,"Total":0}
Effect of Sulfonamide Group Modification on Celecoxib: Molecular Features of Matrix Metalloproteinase Interactive UTX-121 Derivative.
Background/aim: Matrix metalloproteinases (MMPs) are important for extracellular matrix (ECM) degradation with MMP inhibition possibly leading to new antitumor therapies. To examine this possibility, UTX-121, in which the celecoxib sulfonamide was replaced with a methyl ester, was designed to examine the influence of UTX-121 derivatives on MMPs.
Materials and methods: HT-1080 cells were incubated with UTX-121 derivatives over 48 h, and antitumor activities (IC50) were examined using WST-8 assay. The inhibitory effect of UTX-121 derivatives on MMPs in HT-1080 cells was examined using gelatin zymography. Conformational analyses of UTX-121 derivatives were performed using CAChe-Conflex. The interaction of UTX-121 derivatives with MMPs was analyzed using Molegro Virtual Docker.
Results: UTX-121 derivative a2 exhibited enhanced antitumor activity compared to UTX-121. Additionally, derivative a2 demonstrated stronger inhibitory effects on MMP-2, as indicated by reduced band intensity in gelatin zymography, compared to UTX-121. Molecular docking simulations revealed that a2 formed a hydrogen bond with the Tyr366 residue of MMP-2 via the oxygen atom of its methoxy group, supporting its enhanced interaction and inhibitory potency.
Conclusion: UTX-121 derivative a2 showed improved MMP-2 inhibitory activity through specific hydrogen bonding interactions and holds promise as a lead compound for the development of novel MMP-2-targeted anticancer agents.
期刊介绍：
ANTICANCER RESEARCH is an independent international peer-reviewed journal devoted to the rapid publication of high quality original articles and reviews on all aspects of experimental and clinical oncology. Prompt evaluation of all submitted articles in confidence and rapid publication within 1-2 months of acceptance are guaranteed.
ANTICANCER RESEARCH was established in 1981 and is published monthly (bimonthly until the end of 2008). Each annual volume contains twelve issues and index. Each issue may be divided into three parts (A: Reviews, B: Experimental studies, and C: Clinical and Epidemiological studies).
Special issues, presenting the proceedings of meetings or groups of papers on topics of significant progress, will also be included in each volume. There is no limitation to the number of pages per issue.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
