Synthesis and Biological Evaluation of Novel Homoisoflavonoids for Retinal Neovascularization

被引：58

作者：

Basavarajappa, Halesha D. ^{[1
,2
,3
]}

Lee, Bit ^{[6
,7
]}

Lee, Hyungjun ^{[6
,7
]}

Sulaiman, Rania S. ^{[1
,2
,4
,8
]}

An, Hongchan ^{[9
]}

Magana, Carlos ^{[5
]}

Shadmand, Mehdi ^{[1
,2
]}

Vayl, Alexandra ^{[1
,2
]}

Rajashekhar, Gangaraju ^{[1
,2
]}

Kim, Eun-Yeong ^{[10
]}

Suh, Young-Ger ^{[9
]}

Lee, Kiho ^{[10
]}

Seo, Seung-Yong ^{[6
,7
]}

Corson, Timothy W. ^{[1
,2
,3
,4
,5
]}

机构：

[1] Indiana Univ Sch Med, Eugene & Marilyn Glick Eye Inst, Indianapolis, IN 46202 USA

[2] Indiana Univ Sch Med, Dept Ophthalmol, Indianapolis, IN 46202 USA

[3] Indiana Univ Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA

[4] Indiana Univ Sch Med, Dept Pharmacol & Toxicol, Indianapolis, IN 46202 USA

[5] Indiana Univ Sch Med, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46202 USA

[6] Gachon Univ, Coll Pharm, Inchon 406840, South Korea

[7] Gachon Univ, Gachon Inst Pharmaceut Sci, Inchon 406840, South Korea

[8] Cairo Univ, Dept Biochem, Fac Pharm, Cairo 11562, Egypt

[9] Seoul Natl Univ, Coll Pharm, Seoul 151742, South Korea

[10] Korea Univ, Coll Pharm, Sejong, South Korea

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2015年 / 58卷 / 12期

基金：

美国国家卫生研究院; 新加坡国家研究基金会;

关键词：

ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; CELL-PROLIFERATION; IN-VITRO; ANGIOGENESIS; INHIBITION; THERAPY; HYACINTHACEAE; RANIBIZUMAB; BEVACIZUMAB;

D O I：

10.1021/acs.jmedchem.5b00449

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Eye diseases characterized by excessive angiogenesis such as wet age-related macular degeneration, proliferative diabetic retinopathy, and retinopathy of prematurity are major causes of blindness. Cremastranone is an antiangiogenic, naturally occurring homoisoflavanone with efficacy in retinal and choroidal neovascularization models and antiproliferative selectivity for endothelial cells over other cell types. We undertook a cell-based structure activity relationship study to develop more potent cremastranone analogues, with improved antiproliferative selectivity for retinal endothelial cells. Phenylalanyl-incorporated homoisoflavonoids showed improved activity and remarkable selectivity for retinal microvascular endothelial cells. A lead compound inhibited angiogenesis in vitro without inducing apoptosis and had efficacy in the oxygen-induced retinopathy model in vivo.

引用

页码：5015 / 5027

页数：13

共 25 条

[1] Synthesis and Mechanistic Studies of a Novel Homoisoflavanone Inhibitor of Endothelial Cell Growth [J].