期刊
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
卷 35, 期 1, 页码 1674-1684出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/14756366.2020.1809388
关键词
Caspase inhibitor; Isatin sulphonamides; docking studies; Pharmacophore; apoptosis
资金
- National Health and Family Planning Commission of China [2012ZX09304-011, 2013ZX09401003-005, 2013ZX09507001, 2013ZX09507-002]
- Shanghai Science and Technology Development Fund [15DZ2291600]
- Thousand Talents Program in China - Iran National Science Foundation (INSF) [96011863]
ABTRACT In this paper, a new series of isatin-sulphonamide based derivatives were designed, synthesised and evaluated as caspase inhibitors. The compounds containing 1-(pyrrolidinyl)sulphonyl and 2-(phenoxymethyl)pyrrolidin-1-yl)sulphonyl substitution at C5 position of isatin core exhibited better results compared to unsubstituted derivatives. According to the results of caspase inhibitory activity, compound20dshowed moderate inhibitory activity against caspase-3 and -7in vitrocompared to Ac-DEVD-CHO (IC50= 0.016 +/- 0.002 mu M). Among the studied compounds, some active inhibitors with IC(50s)in the range of 2.33-116.91 mu M were identified. The activity of compound20dwas rationalised by the molecular modelling studies exhibiting the additional van der Waals interaction of N-phenylacetamide substitution along with efficacious T-shaped pi-pi and pi-cation interactions. The introduction of compound20dwith good caspase inhibitory activity will help researchers to find more potent agents.
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