Discovery of a natural product-like c-myc G-quadruplex DNA groove-binder by molecular docking.

The natural product-like carbamide (1) has been identified as a stabilizer of the c-myc G-quadruplex through high-throughput virtual screening. NMR and molecular modeling experiments revealed a groove-binding mode for 1. The biological activity of 1 against the c-myc G-quadruplex was confirmed by it...

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Autores principales: Dik-Lung Ma, Daniel Shiu-Hin Chan, Wai-Chung Fu, Hong-Zhang He, Hui Yang, Siu-Cheong Yan, Chung-Hang Leung
Formato: article
Lenguaje:EN
Publicado: Public Library of Science (PLoS) 2012
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Acceso en línea:https://doaj.org/article/31827df75904473e9e38d151e3ca860b
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Sumario:The natural product-like carbamide (1) has been identified as a stabilizer of the c-myc G-quadruplex through high-throughput virtual screening. NMR and molecular modeling experiments revealed a groove-binding mode for 1. The biological activity of 1 against the c-myc G-quadruplex was confirmed by its ability to inhibit Taq polymerase-mediated DNA extension and c-myc expression in vitro, demonstrating that 1 is able to control c-myc gene expression at the transcriptional level presumably through the stabilization of the c-myc promoter G-quadruplex. Furthermore, the interaction between carbamide analogues and the c-myc G-quadruplex was also investigated by in vitro experiments in order to generate a brief structure-activity relationship (SAR) for the observed potency of carbamide 1.