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Targeting the c-Kit Promoter G-quadruplexes with 6-Substituted Indenoisoquinolines.

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.

SUBMITTER: Bejugam M

PROVIDER: S-EPMC4017300 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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Targeting the c-Kit Promoter G-quadruplexes with 6-Substituted Indenoisoquinolines.

Bejugam Mallesham M Gunaratnam Mekala M Müller Sebastian S Sanders Deborah A DA Sewitz Sven S Fletcher Jonathan A JA Neidle Stephen S Balasubramanian Shankar S

ACS medicinal chemistry letters 20100701 7

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, whi ...[more]

PMID: 24900212

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