Discovery, synthesis and biological evaluation of 2-(4-(N-phenethylsulfamoyl)phenoxy)acetamides (SAPAs) as novel sphingomyelin synthase 1 inhibitors

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	Discovery, synthesis and biological evaluation of 2-(4-(N-phenethylsulfamoyl)phenoxy)acetamides (SAPAs) as novel sphingomyelin synthase 1 inhibitors
	Li YL(李亚莉)1; Qi XY(齐翔宇)1; Jiang H(蒋慧)1; Deng XD(邓小东)1; Dong YP(董艳萍)1; Ding YB(丁延波)1; Zhou L(周璐)1; Men P(门鹏)1; Chu Y(楚勇)1; Wang RX(王任小)1
刊名	Bioorg. Med. Chem.
	2015
卷号	23 期号:18 页码:6173-6184
其他题名	新型的鞘磷脂合酶抑制剂2-(4-(N-苯乙基氨磺酰基)苯氧基)乙酰胺 (SAPAs)的发现, 合成和生物学评价
通讯作者	王任小 ; 叶德泳
英文摘要	Sphingomyelin synthase (SMS) has been proved to be a potential drug target for the treatment of atherosclerosis. However, few SMS inhibitors have been reported. In this paper, structure-based virtual screening was performed on hSMS1. SAPA 1a was discovered as a novel SMS1 inhibitor with an IC50 value of 5.2 mu M in enzymatic assay. A series of 2-(4-(N-phenethylsulfamoyl)phenoxy)acetamides (SAPAs) were synthesized and their biological activities toward SMS1 were evaluated. Among them, SAPA 1j was found to be the most potent SMS1 inhibitor with an IC50 value of 2.1 mu M in in vitro assay. The molecular docking studies suggested the interaction modes of SMS1 inhibitors and PC with the active site of SMS1. Site-directed mutagenesis validated the involvement of residues Arg342 and Tyr338 in enzymatic sphingomyelin production. The discovery of SAPA derivatives as a novel class of SMS1 inhibitors would advance the development of more effective SMS1 inhibitors. (c) 2015 Elsevier Ltd. All rights reserved.
学科主题	计算机化学
收录类别	SCI
原文出处	http://dx.doi.org/10.1016/j.bmc.2015.07.060
语种	英语
WOS记录号	WOS:000360910000010
内容类型	期刊论文
源URL	[http://ir.sioc.ac.cn/handle/331003/39824]
专题	上海有机化学研究所_计算机化学与化学信息学研究室
作者单位	1.复旦大学 2.中科院上海有机化学研究所, 生命有机化学国家重点实验室
推荐引用方式 GB/T 7714	Li YL,Qi XY,Jiang H,et al. Discovery, synthesis and biological evaluation of 2-(4-(N-phenethylsulfamoyl)phenoxy)acetamides (SAPAs) as novel sphingomyelin synthase 1 inhibitors[J]. Bioorg. Med. Chem.,2015,23(18):6173-6184.
APA	李亚莉.,齐翔宇.,蒋慧.,邓小东.,董艳萍.,...&叶德泳.(2015).Discovery, synthesis and biological evaluation of 2-(4-(N-phenethylsulfamoyl)phenoxy)acetamides (SAPAs) as novel sphingomyelin synthase 1 inhibitors.Bioorg. Med. Chem.,23(18),6173-6184.
MLA	李亚莉,et al."Discovery, synthesis and biological evaluation of 2-(4-(N-phenethylsulfamoyl)phenoxy)acetamides (SAPAs) as novel sphingomyelin synthase 1 inhibitors".Bioorg. Med. Chem. 23.18(2015):6173-6184.