An antiangiogenic homoisoflavanone, cremastranone, was synthesized for the first time. This scalable synthesis, which includes selective demethylation, could be used to develop lead molecules to treat angiogenesis-induced eye diseases. Synthetic cremastranone inhibited the proliferation, migration and tube formation ability of human retinal microvascular endothelial cells, important steps in pathological angiogenesis.
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http://dx.doi.org/10.1039/c4ob01604a | DOI Listing |
Pharmaceutics
October 2022
College of Pharmacy, Korea University, Sejong 30019, Korea.
J Org Chem
August 2019
College of Pharmacy , Gachon University, Incheon 21936 , Republic of Korea.
Neovascular eye diseases are a major cause of blindness. Excessive angiogenesis is a feature of several conditions, including wet age-related macular degeneration, proliferative diabetic retinopathy, and retinopathy of prematurity. Development of novel antiangiogenic small molecules for the treatment of neovascular eye disease is essential to provide new therapeutic leads for these diseases.
View Article and Find Full Text PDFMolecules
August 2016
College of Pharmacy and Gachon Institute of Pharmaceutical Sciences, Gachon University, Incheon 21936, Korea.
Naturally occurring homoisoflavonoids containing either 5,7-dihydroxy-6-methoxy or 7-hydroxy-5,6-dimethoxy groups such as the antiangiogenic homoisoflavanone, cremastranone, were synthesized via three or four linear steps from the known 4-chromenone. This facile synthesis includes chemoselective 1,4-reduction of 4-chromenone and selective deprotection of 3-benzylidene-4-chromanone a containing C7-benzyloxy group.
View Article and Find Full Text PDFJ Med Chem
June 2015
Eugene and Marilyn Glick Eye Institute, Indiana University School of Medicine, Indianapolis, Indiana 46202, United States.
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.
View Article and Find Full Text PDFExp Eye Res
December 2014
Eugene and Marilyn Glick Eye Institute, Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, IN, United States; Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN, United States; Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, United States; Melvin and Bren Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN, United States. Electronic address:
Natural products are characterized by high chemical diversity and biochemical specificity; therefore, they are appealing as lead compounds for drug discovery. Given the importance of angiogenesis to many pathologies, numerous natural products have been explored as potential anti-angiogenic drugs. Ocular angiogenesis underlies blinding eye diseases such as retinopathy of prematurity (ROP) in children, proliferative diabetic retinopathy (DR) in adults of working age, and age-related macular degeneration (AMD) in the elderly.
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