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Discovery, synthesis and biological evaluation of 2-(4-(N-phenethylsulfamoyl)phenoxy)acetamides (SAPAs) as novel sphingomyelin synthase 1 inhibitors
Alternative Title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
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; Jiang XC(蒋宪成)1; Ye DY(叶德泳)1
2015
Source PublicationBioorg. Med. Chem.
Volume23Issue:18Pages:6173-6184
AbstractSphingomyelin 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.
Subtype论文
Subject Area计算机化学
DOI10.1016/j.bmc.2015.07.060
URL查看原文
Indexed BySCI
Language英语
WOS IDWOS:000360910000010
Citation statistics
Cited Times:9[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.sioc.ac.cn/handle/331003/39824
Collection计算机化学与化学信息学研究室
Corresponding AuthorWang RX(王任小); Ye DY(叶德泳)
Affiliation1.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
Recommended Citation
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.
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