title: Disubstituted quinazoline derivatives as a new type of highly selective ligands for telomeric G-quadruplex DNA.
abstract: A series of 2,4-disubstituted quinazoline derivatives found to be a new type of highly selective ligand to bind with telomeric G-quadruplex DNA, and their biological properties were reported for the first time.Their interactions with telomeric G-quadruplex DNA were evaluated by using fluorescence resonance energy transfer (FRET) melting assay, circular dichroism (CD) spectroscopy, surface plasmon resonance (SPR), nuclear magnetic resonance (NMR), and molecular modeling. Our results showed that these derivatives could well recognize G-quadruplex and have high selectivity toward G-quadruplex over duplex DNA. The structure-activity relationships (SARs) study revealed that the disubstitution of quinazoline and the length of the amide side chain were important for its interaction with the G-quadruplex. Furthermore, telomerase inhibition of the quinazoline derivatives and their cellular effects were studied.
authors: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, People's Republic of China.
authors: Zeng
authors: Z
authors: Li
authors: Jia-Heng
authors: JH
authors: Tan
authors: Jin-Hui
authors: JH
authors: He
authors: Yi
authors: Y
authors: Long
authors: Tian-Miao
authors: TM
authors: Ou
authors: Ding
authors: D
authors: Li
authors: Lian-Quan
authors: LQ
authors: Gu
authors: Zhi-Shu
authors: ZS
authors: Huang
mesh_terms: D001483:Base Sequence; D004247:DNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D054856:G-Quadruplexes / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D011799:Quinazolines / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D013057:Spectrum Analysis; D019098:Telomerase / Q000037:antagonists & inhibitors; D016615:Telomere / Q000187:drug effects / Q000235:genetics*; D059506:Telomere Shortening / Q000187:drug effects
chemical_list: D008024:Ligands; D011799:Quinazolines; D004247:DNA; D019098:Telomerase