Browsing by Author "Lee, Hyungjun"

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    Design, synthesis and biological evaluation of photoaffinity probes of antiangiogenic homoisoflavonoids
    (Elsevier, 2016-09) Lee, Bit; Sun, Wei; Lee, Hyungjun; Basavarajappa, Halesha; Sulaiman, Rania S.; Sishtla, Kamakshi; Fei, Xiang; Corson, Timothy W.; Seo, Seung-Yong; Department of Ophthalmology, IU School of Medicine
    A naturally occurring homoisoflavonoid, cremastranone (1) inhibited angiogenesis in vitro and in vivo. We developed an analogue SH-11037 (2) which is more potent than cremastranone in human retinal microvascular endothelial cells (HRECs) and blocks neovascularization in animal models. Despite their efficacy, the mechanism of these compounds is not yet fully known. In the course of building on a strong foundation of SAR and creating a novel chemical tool for target identification of homoisoflavonoid-binding proteins, various types of photoaffinity probes were designed and synthesized in which benzophenone and biotin were attached to homoisoflavanonoids using PEG linkers on either the C-3′ or C-7 position. Notably, the photoaffinity probes linking on the phenol group of the C-3′ position retain excellent activity of inhibiting retinal endothelial cell proliferation with up to 72 nM of GI50.
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    Synthesis and Biological Evaluation of Novel Homoisoflavonoids for Retinal Neovascularization
    (ACS, 2015-06) Basavarajappa, Halesha D.; Lee, Bit; Lee, Hyungjun; Sulaiman, Rania S.; An, Hongchan; Magaña, Carlos; Shadmand, Mehdi; Vayl, Alexandra; Rajashekhar, Gangaraju; Kim, Eun-Yeong; Suh, Young-Ger; Lee, Kiho; Seo, Seung-Yong; Corson, Timothy W.; Department of Ophthalmology, IU School of Medicine
    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.
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    Synthesis of Natural Homoisoflavonoids Having Either 5,7-Dihydroxy-6-methoxy or 7-Hydroxy-5,6-dimethoxy Groups
    (MDPI, 2016-08) Lee, Hyungjun; Yuan, Yue; Rhee, Inmoo; Corson, Timothy W.; Seo, Seung-Yong; Department of Ophthalmology, IU School of Medicine
    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.