title: Synthesis and Biological Evaluation of Novel Homoisoflavonoids for Retinal Neovascularization.
abstract: 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.
authors.affiliation: Eugene and Marilyn Glick Eye Institute, Indiana University School of Medicine, Indianapolis, Indiana 46202, United States.|Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana 46202, United States.|Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, United States.
authors.forename: Halesha D
authors.initials: HD
authors.lastname: Basavarajappa
authors.affiliation: College of Pharmacy and Gachon Institute of Pharmaceutical Sciences, Gachon University, Incheon 406-840, South Korea.
authors.forename: Bit
authors.initials: B
authors.lastname: Lee
authors.affiliation: College of Pharmacy and Gachon Institute of Pharmaceutical Sciences, Gachon University, Incheon 406-840, South Korea.
authors.forename: Hyungjun
authors.initials: H
authors.lastname: Lee
authors.affiliation: Eugene and Marilyn Glick Eye Institute, Indiana University School of Medicine, Indianapolis, Indiana 46202, United States.|Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana 46202, United States.|Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana 46202, United States.|Department of Biochemistry, College of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Rania S
authors.initials: RS
authors.lastname: Sulaiman
authors.affiliation: College of Pharmacy, Seoul National University, Seoul, South Korea.
authors.forename: Hongchan
authors.initials: H
authors.lastname: An
authors.affiliation: Melvin and Bren Simon Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana 46202, United States.
authors.forename: Carlos
authors.initials: C
authors.lastname: Magaña
authors.affiliation: Eugene and Marilyn Glick Eye Institute, Indiana University School of Medicine, Indianapolis, Indiana 46202, United States.|Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana 46202, United States.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Shadmand
authors.affiliation: Eugene and Marilyn Glick Eye Institute, Indiana University School of Medicine, Indianapolis, Indiana 46202, United States.|Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana 46202, United States.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Vayl
authors.affiliation: Eugene and Marilyn Glick Eye Institute, Indiana University School of Medicine, Indianapolis, Indiana 46202, United States.|Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana 46202, United States.
authors.forename: Gangaraju
authors.initials: G
authors.lastname: Rajashekhar
authors.affiliation: College of Pharmacy, Korea University, Sejong, South Korea.
authors.forename: Eun-Yeong
authors.initials: EY
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Seoul National University, Seoul, South Korea.
authors.forename: Young-Ger
authors.initials: YG
authors.lastname: Suh
authors.affiliation: College of Pharmacy, Korea University, Sejong, South Korea.
authors.forename: Kiho
authors.initials: K
authors.lastname: Lee
authors.affiliation: College of Pharmacy and Gachon Institute of Pharmaceutical Sciences, Gachon University, Incheon 406-840, South Korea.
authors.forename: Seung-Yong
authors.initials: SY
authors.lastname: Seo
authors.affiliation: Eugene and Marilyn Glick Eye Institute, Indiana University School of Medicine, Indianapolis, Indiana 46202, United States.|Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana 46202, United States.|Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, United States.|Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana 46202, United States.|Melvin and Bren Simon Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana 46202, United States.
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Corson
mesh_terms: D020533:Angiogenesis Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D007529:Isoflavones / Q000737:chemistry* / Q000494:pharmacology*; D051379:Mice; D012160:Retina / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D015861:Retinal Neovascularization / Q000188:drug therapy* / Q000473:pathology
chemical_list: C524883:5,7-dihydroxy-3-(3-hydroxy-4-methoxybenzyl)-6-methoxychroman-4-one; D020533:Angiogenesis Inhibitors; D007529:Isoflavones