[基于二氢吡啶-2- 1支架的新型组蛋白去乙酰化酶抑制剂的合成及抗肿瘤活性]。

药学学报 Pub Date : 2016-11-01

Jia-qing Li, Xiao Han

{"title":"[基于二氢吡啶-2- 1支架的新型组蛋白去乙酰化酶抑制剂的合成及抗肿瘤活性]。","authors":"Jia-qing Li, Xiao Han","doi":"","DOIUrl":null,"url":null,"abstract":"To discover novel dihydropyridin-2-one derivatives with higher HDAC inhibitory activity and subtype selectivity, twenty-seven dihydropyridin-2-one derivatives containing triazole unit were synthesized via click chemistry. The structures of these compounds have been confirmed by IR, 1H NMR and HR-MS spectra. Preliminary in vitro pharmacological tests showed that these compounds potently inhibited HDAC1 and HDAC6, which also displayed significant antiproliferative effect on five cancer cells, and most of them were better than that of the parent compound 1A and drug SAHA. Specifically, compound 18g exhibited most potent anti-HDAC1 activity, and also showed the greatest potency against PC-3 and Hep G2. Additionally, all compounds were nontoxic to health RWPE-1 and VERO cells, while SAHA showed essential toxicity.","PeriodicalId":35924,"journal":{"name":"药学学报","volume":"51 11","pages":"1734-44"},"PeriodicalIF":0.0000,"publicationDate":"2016-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"[Synthesis and anti-tumor activity of novel histone deacetylase inhibitors based on dihydropyridin-2-one scaffold].\",\"authors\":\"Jia-qing Li, Xiao Han\",\"doi\":\"\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"To discover novel dihydropyridin-2-one derivatives with higher HDAC inhibitory activity and subtype selectivity, twenty-seven dihydropyridin-2-one derivatives containing triazole unit were synthesized via click chemistry. The structures of these compounds have been confirmed by IR, 1H NMR and HR-MS spectra. Preliminary in vitro pharmacological tests showed that these compounds potently inhibited HDAC1 and HDAC6, which also displayed significant antiproliferative effect on five cancer cells, and most of them were better than that of the parent compound 1A and drug SAHA. Specifically, compound 18g exhibited most potent anti-HDAC1 activity, and also showed the greatest potency against PC-3 and Hep G2. Additionally, all compounds were nontoxic to health RWPE-1 and VERO cells, while SAHA showed essential toxicity.\",\"PeriodicalId\":35924,\"journal\":{\"name\":\"药学学报\",\"volume\":\"51 11\",\"pages\":\"1734-44\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2016-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"药学学报\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"药学学报","FirstCategoryId":"1085","ListUrlMain":"","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

为寻找具有较高HDAC抑制活性和亚型选择性的新型二氢吡啶-2- 1衍生物，采用click化学方法合成了27个含三唑单元的二氢吡啶-2- 1衍生物。这些化合物的结构经IR、1H NMR和HR-MS确证。初步体外药理实验表明，这些化合物对HDAC1和HDAC6均有较强的抑制作用，对5种肿瘤细胞均有明显的抗增殖作用，且多数优于母体化合物1A和药物SAHA。具体而言，化合物18g表现出最有效的抗hdac1活性，并且对PC-3和Hep G2也表现出最大的效力。此外，所有化合物都对健康的RWPE-1和VERO细胞无毒，而SAHA显示出必要的毒性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

本刊更多论文

[Synthesis and anti-tumor activity of novel histone deacetylase inhibitors based on dihydropyridin-2-one scaffold].

To discover novel dihydropyridin-2-one derivatives with higher HDAC inhibitory activity and subtype selectivity, twenty-seven dihydropyridin-2-one derivatives containing triazole unit were synthesized via click chemistry. The structures of these compounds have been confirmed by IR, 1H NMR and HR-MS spectra. Preliminary in vitro pharmacological tests showed that these compounds potently inhibited HDAC1 and HDAC6, which also displayed significant antiproliferative effect on five cancer cells, and most of them were better than that of the parent compound 1A and drug SAHA. Specifically, compound 18g exhibited most potent anti-HDAC1 activity, and also showed the greatest potency against PC-3 and Hep G2. Additionally, all compounds were nontoxic to health RWPE-1 and VERO cells, while SAHA showed essential toxicity.

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

药学学报 Pharmacology, Toxicology and Pharmaceutics-Pharmacology, Toxicology and Pharmaceutics (all)

CiteScore

1.20

自引率

0.00%

发文量

期刊介绍： Acta Pharmaceutica Sinica B (APSB) is a bimonthly English peer-reviewed online journal in ScienceDirect, which publishes significant original research articles, communications and high quality reviews of recent advances. APSB encourages submissions from all areas of pharmaceutical sciences, including pharmacology, pharmaceutics, medicinal chemistry, natural products, pharmacognosy, pharmaceutical analysis and pharmacokinetics. APSB is a part of the series Acta Pharmaceutica Sinica, which was founded in 1953. The journal is co-published by Elsevier B.V., in association with the Institute of MateriaMedica, Chinese Academy of Medical Sciences and Chinese Pharmaceutical Association.