Authors:
M Bejugam, M Gunaratnam, S Müller, DA Sanders, S Sewitz, JA Fletcher, S Neidle, S Balasubramanian
Journal name: 
ACS Med Chem Lett
Citation info: 
1(7):306-310
Abstract: 
Herein, we demonstrate the design, synthesis, biophysical properties, and preliminary biological evaluation of 6-substituted indenoisoquinolines as a new class of G-quadruplex stabilizing small molecule ligands. We have synthesized 6-substituted indenoisoquinolines 1a-e in two steps from commercially available starting materials with excellent yields. The G-quadruplex stabilization potential of indenoisoquinolines 1a-e was evaluated by fluorescence resonance energy transfer-melting analysis, which showed that indenoisoquinolines show a high level of stabilization of various G-quadruplex DNA structures. Indenoisoquinolines demonstrated potent inhibition of cell growth in the GIST882 patient-derived gastrointestinal stromal tumor cell line, accompanied by inhibition of both c-Kit transcription and KIT oncoprotein levels.
DOI: 
http://doi.org/10.1021/ml100062z
Research group: 
Balasubramanian Group
E-pub date: 
14 Oct 2010