Synthesis and anti-tumor activity of novel histone deacetylase inhibitors based on dihydropyridin-2-one scaffold
10.16438/j.0513-4870.2016-0503
- VernacularTitle:二氢吡啶酮类组蛋白去乙酰化酶抑制剂的设计、合成及抗肿瘤活性
- Author:
Jia-qing LI
1
;
Xiao HAN
1
Author Information
1. Department of Biological Medicine, Changjiang Polytechnic, Wuhan 430064, China
- Publication Type:ORIGINAL ARTICLES
- Keywords:
dihydropyridin-2-one;
click chemistry;
histone deacetylase inhibitor;
anti-tumor activity
- From:
Acta Pharmaceutica Sinica
2016;51(11):1734-
- CountryChina
- Language:Chinese
-
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 HepG2. Additionally, all compounds were nontoxic to health RWPE-1 and VERO cells, while SAHA showed essential toxicity.
