期刊
JOURNAL OF MEDICINAL CHEMISTRY
卷 60, 期 4, 页码 1292-1308出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jmedchem.6b01218
关键词
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资金
- Natural Science Foundation of China [81330077, 21172272, 91213302, 21372263]
- Foundation for Distinguished Young Talents in Higher Education of Guangdong [Yq2013002]
- Guangdong Provincial Key Laboratory of Construction Foundation [2011A060901014]
Transcriptional control of c-myc oncogene is an important strategy for antitumor drug design. G-quadruplexes in the promoter region have been proven to be the factor NM23-H2 can reactivate c-myc transcription by transcriptional down-regulator of this gene. The transcriptional unwinding the G-quadruplex structure. Thus, down-regulation of c-myc transcription via disrupting G-quadruplex-NM23-H2 interaction might be a potential approach for cancer therapy. Here, a series of new isaindigotone derivatives were designed and synthesized based on our previous study. The abilities of these derivatives on interacting with G-quadruplexes or NM23-H2, and disrupting G-quadruplex-NM23-H2 interaction were evaluated. Among these derivatives, 19d and 22d showed remarkable abilities on disrupting G-quadruplex-NM23-H2 interaction. They exhibited significant effects on c-myc-relating processes in SiHa cells, including inhibiting the transcription and translation, inhibiting cellular proliferation, inducing apoptosis, and regulating cell cycle. Our findings provided the basis for the anticancer strategy based on c-myc transcriptional regulation via small molecules disrupting G-quadruplex-protein interaction.
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