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

Bioorg Med Chem Lett

College of Pharmacy and Gachon Institute of Pharmaceutical Sciences, Gachon University, Incheon 21936, South Korea. Electronic address:

Published: September 2016

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 72nM of GI50.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5129841PMC
http://dx.doi.org/10.1016/j.bmcl.2016.07.043DOI Listing

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