3 years ago

Discovery of Novel 11-Triazole Substituted Benzofuro[3,2-b]quinolone Derivatives as c-myc G-Quadruplex Specific Stabilizers via Click Chemistry

Discovery of Novel 11-Triazole Substituted Benzofuro[3,2-b]quinolone Derivatives as c-myc G-Quadruplex Specific Stabilizers via Click Chemistry
Wang Peng, Jia-Heng Tan, Ming-Hao Hu, Tian-Miao Ou, Zhi-Shu Huang, Lian-Quan Gu, Xiao-Xuan Su, Qi Zhang, Shu-Ling Lin, Guo-Tao Kuang, Honggen Wang, Shi-Ke Wang, De-Ying Zeng
The specificity of nucleic acids’ binders is crucial for developing this kind of drug, especially for novel G-quadruplexes’ binders. Quindoline derivatives have been developed as G-quadruplex stabilizers with good interactive activities. In order to improve the selectivity and binding affinity of quindoline derivatives as c-myc G-quadruplex binding ligands, novel triazole containing benzofuroquinoline derivatives (T-BFQs) were designed and synthesized by using the 1,3-dipolar cycloaddition of a series of alkyne and azide building blocks. The selectivity toward c-myc G-quadruplex DNA of these novel T-BFQs was significantly improved, together with an obvious increase on binding affinity. Further cellular and in vivo experiments indicated that the T-BFQs showed inhibitory activity on tumor cells’ proliferation, presumably through the down-regulation of transcription of c-myc gene. Our findings broadened the modification strategies of specific G-quadruplex stabilizers.

Publisher URL: http://dx.doi.org/10.1021/acs.jmedchem.7b00016

DOI: 10.1021/acs.jmedchem.7b00016

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