Design, synthesis and biological evaluation of photoaffinity probes of antiangiogenic homoisoflavonoids

Bit Lee, Wei Sun, Hyungjun Lee, Halesha Basavarajappa, Rania S. Sulaiman, Kamakshi Sishtla, Xiang Fei, Timothy Corson, Seung Yong Seo

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4277-4281
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume26
Issue number17
DOIs
StatePublished - Sep 1 2016

Keywords

  • Antiangiogenic agents
  • Homoisoflavonoids
  • Human retinal microvascular endothelial cells
  • Photoaffinity probes
  • Wet age-related macular degeneration

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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