{"title":"Synthesis of 2-Aryl(alkyl)benzimidazole Hydroxamic Acids as HDAC Inhibitors with Anti-Angiogenesis Properties.","authors":"Yi-Ting Liu, Cheng-Ta Lai, Shih-Wei Wang, Shan-Chi Liu, Yi-Lin Hwang, Yi-Chen Tsai, Chi-Yeh Lee, Yu-Wei Lai, Juei-Yu Yen, Po-Chuan Wang, Hsueh-Yun Lee","doi":"10.1002/cmdc.202500984","DOIUrl":null,"url":null,"abstract":"<p><p>This study synthesized a series of C2 and N1-substituted benzimidazole hydroxamic acid (6-19) as HDAC inhibitors. Among them, most of 2-aryl(alkyl)benzimidazole hydroxamic acids (11-16) exhibited HDAC6 activity and slight HDAC1 (or HDAC2) activity. In addition, they also showed anti-angiogenic activity and inhibited the growth of tested cancer cells. For instance, compound 13 has a GI<sub>50</sub> of 3.9 μM against EPCs and inhibited the growth of HCT-116, SK-Hep-1, and PC-3 cells with GI<sub>50</sub> values of 1.3, 4.2, and 7.5 μM, respectively. The exact mechanism underlying the anti-angiogenic effects of these compounds remains unknown, though this study gives an insight into how future HDAC inhibitors that aim to target blood vessel formation can be designed.</p>","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"21 8","pages":"e202500984"},"PeriodicalIF":3.4000,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13128345/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ChemMedChem","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/cmdc.202500984","RegionNum":4,"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
Abstract
This study synthesized a series of C2 and N1-substituted benzimidazole hydroxamic acid (6-19) as HDAC inhibitors. Among them, most of 2-aryl(alkyl)benzimidazole hydroxamic acids (11-16) exhibited HDAC6 activity and slight HDAC1 (or HDAC2) activity. In addition, they also showed anti-angiogenic activity and inhibited the growth of tested cancer cells. For instance, compound 13 has a GI50 of 3.9 μM against EPCs and inhibited the growth of HCT-116, SK-Hep-1, and PC-3 cells with GI50 values of 1.3, 4.2, and 7.5 μM, respectively. The exact mechanism underlying the anti-angiogenic effects of these compounds remains unknown, though this study gives an insight into how future HDAC inhibitors that aim to target blood vessel formation can be designed.
期刊介绍：
Quality research. Outstanding publications. With an impact factor of 3.124 (2019), ChemMedChem is a top journal for research at the interface of chemistry, biology and medicine. It is published on behalf of Chemistry Europe, an association of 16 European chemical societies.
ChemMedChem publishes primary as well as critical secondary and tertiary information from authors across and for the world. Its mission is to integrate the wide and flourishing field of medicinal and pharmaceutical sciences, ranging from drug design and discovery to drug development and delivery, from molecular modeling to combinatorial chemistry, from target validation to lead generation and ADMET studies. ChemMedChem typically covers topics on small molecules, therapeutic macromolecules, peptides, peptidomimetics, and aptamers, protein-drug conjugates, nucleic acid therapies, and beginning 2017, nanomedicine, particularly 1) targeted nanodelivery, 2) theranostic nanoparticles, and 3) nanodrugs.
Contents
ChemMedChem publishes an attractive mixture of:
Full Papers and Communications
Reviews and Minireviews
Patent Reviews
Highlights and Concepts
Book and Multimedia Reviews.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
