Disubstituted quinazoline derivatives as a new type of highly selective ligands for telomeric G-quadruplex DNA.

Research paper by Zeng Z Li, Jia-Heng JH Tan, Jin-Hui JH He, Yi Y Long, Tian-Miao TM Ou, Ding D Li, Lian-Quan LQ Gu, Zhi-Shu ZS Huang

Indexed on: 23 Nov '11Published on: 23 Nov '11Published in: European Journal of Medicinal Chemistry


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.

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