Quinazoline derivative QPB-15e stabilizes the c-myc promoter G-quadruplex and inhibits tumor growth in vivo.
作者： Zeng Li , Chen Liu , Cheng Huang , Xiaoming Meng , Lei Zhang
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摘要: // Zeng Li 1 , Chen Liu Cheng Huang Xiaoming Meng Lei Zhang Jinhui He 2 Jun School of Pharmacy, Anhui Medical University, Hefei 230032, China Pharmaceutical Sciences, Sun Yat-sen Guangzhou University City, 510006, Correspondence to: Li, email: jl3849@sohu.com Keywords: c-myc, G-quadruplex, quinazoline derivative, QPB-15e, anti-tumor Received: March 06, 2016 Accepted: April 16, Published: 28, 2016 ABSTRACT The ribozyme-sensitive element NHE-III1 in the P1 promoter region important proto-oncogene c-myc contains many guanine (G)-rich sequences. Induction and stabilization G-quadruplex formed by can downregulate expression. In present study, we found that a derivative designed synthesized our laboratory, binds to stabilizes vitro thereby inhibiting double-stranded DNA replication, downregulating gene expression arresting cancer cell proliferation. PCR termination experiments showed QPB-15e blocked replication inducing or stabilizing G-quadruplex. FRET-melting further confirmed improved stability CD spectroscopy indicated compound interacted directly with G-rich sequence. competitive dialysis experiments, bound preferentially quadruplex various structures, especially within region. Moreover, reduced weights volumes tumors transplanted into nude mice. These findings strongly suggest is ligand properties, may be efficacious for treating humans.
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