Trisubstituted Isoalloxazines as a New Class of G-Quadruplex Binding Ligands: Small Molecule Regulation of c-kit Oncogene Expression

Herein, we report the design, synthesis, biophysical evaluation with primary biological data of 3,8,10-trisubstituted isoalloxazines as a new class of G-quadruplex binding ligands. We have developed a short and robust synthesis for trisubstituted isoalloxazines in good yields. The G-quadruplex bindi...

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Published inJournal of the American Chemical Society Vol. 129; no. 43; pp. 12926 - 12927
Main Authors Bejugam, Mallesham, Sewitz, Sven, Shirude, Pravin S, Rodriguez, Raphael, Shahid, Ramla, Balasubramanian, Shankar
Format Journal Article
LanguageEnglish
Published 01.01.2007
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Summary:Herein, we report the design, synthesis, biophysical evaluation with primary biological data of 3,8,10-trisubstituted isoalloxazines as a new class of G-quadruplex binding ligands. We have developed a short and robust synthesis for trisubstituted isoalloxazines in good yields. The G-quadruplex binding and stabilization potential of isoalloxazines was assessed by surface plasmon resonance and fluorescence resonance energy transfer assay. The data revealed that these isoalloxazines bind and stabilize G-quadruplex DNA, but not duplex DNA, and exhibit potential for discriminating between DNA quadruplexes. Cell-based experiments using cell lines that express the proto- oncogene c-kit (MCF-7 and HGC-27) showed that such isoalloxazines can inhibit the expression of c-kit.
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ISSN:1272-7863
1520-5126
DOI:10.1021/ja075881pPII:S0002-7863(07)05881-7