Efficient synthesis, biological evaluation, and docking study of isatin based derivatives as caspase inhibitors

doi:10.1080/14756366.2020.1809388

	Efficient synthesis, biological evaluation, and docking study of isatin based derivatives as caspase inhibitors
	Firoozpour, Loghman 1; Gao, Lixin 2; Moghimi, Setareh 1; Pasalar, Parvin 3; Davoodi, Jamshid 4; Wang, Ming-Wei 2; Rezaei, Zahra 5; Dadgar, Armin 6; Yahyavi, Hoda 1; Amanlou, Massoud 5
刊名	JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
	2020
卷号	35 期号:1 页码:1674-1684
关键词	Caspase inhibitor Isatin sulphonamides docking studies Pharmacophore apoptosis
ISSN号	1475-6366
DOI	10.1080/14756366.2020.1809388
通讯作者	Firoozpour, Loghman(firoozpour@gmail.com) ; Foroumadi, Alireza(aforoumadi@yahoo.com)
英文摘要	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.
资助项目	National Health and Family Planning Commission of China[2012ZX09304-011] ; National Health and Family Planning Commission of China[2013ZX09401003-005] ; National Health and Family Planning Commission of China[2013ZX09507001] ; National Health and Family Planning Commission of China[2013ZX09507-002] ; Shanghai Science and Technology Development Fund[15DZ2291600] ; Thousand Talents Program in China - Iran National Science Foundation (INSF)[96011863]
WOS关键词	SELECTIVE NONPEPTIDE INHIBITORS ; APOPTOSIS ; POTENT ; DISCOVERY ; 4-ARYL-4H-CHROMENES ; PET ; ACTIVATION ; SCAFFOLD ; DESIGN ; SERIES
WOS研究方向	Biochemistry & Molecular Biology ; Pharmacology & Pharmacy
语种	英语
出版者	TAYLOR & FRANCIS LTD
WOS记录号	WOS:000562502300001
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/292483]
专题	中国科学院上海药物研究所
通讯作者	Firoozpour, Loghman; Foroumadi, Alireza
作者单位	1.Univ Tehran Med Sci, Inst Pharmaceut Sci TIPS, Drug Design & Dev Res Ctr, Tehran, Iran 2.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, Shanghai, Peoples R China 3.Univ Tehran Med Sci, Fac Med, Dept Biochem, Tehran, Iran 4.Univ Tehran, Inst Biochem & Biophys, Tehran, Iran 5.Univ Tehran Med Sci, Fac Pharm, Dept Med Chem, Tehran, Iran 6.Kermanshah Univ Med Sci, Pharmaceut Sci Res Ctr, Kermanshah, Iran
推荐引用方式 GB/T 7714	Firoozpour, Loghman,Gao, Lixin,Moghimi, Setareh,et al. Efficient synthesis, biological evaluation, and docking study of isatin based derivatives as caspase inhibitors[J]. JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY,2020,35(1):1674-1684.
APA	Firoozpour, Loghman.,Gao, Lixin.,Moghimi, Setareh.,Pasalar, Parvin.,Davoodi, Jamshid.,...&Foroumadi, Alireza.(2020).Efficient synthesis, biological evaluation, and docking study of isatin based derivatives as caspase inhibitors.JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY,35(1),1674-1684.
MLA	Firoozpour, Loghman,et al."Efficient synthesis, biological evaluation, and docking study of isatin based derivatives as caspase inhibitors".JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY 35.1(2020):1674-1684.