School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, People's Republic of China.
Eur J Med Chem. 2012 Jan;47(1):299-311. doi: 10.1016/j.ejmech.2011.10.057. Epub 2011 Nov 7.
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.
一系列 2,4-二取代喹唑啉衍生物被发现是一种与端粒 G-四链体 DNA 结合的新型高选择性配体，这是它们的生物特性首次被报道。通过荧光共振能量转移（FRET）熔解实验、圆二色性（CD）光谱、表面等离子体共振（SPR）、核磁共振（NMR）和分子建模等方法评估了它们与端粒 G-四链体 DNA 的相互作用。研究结果表明，这些衍生物能够很好地识别 G-四链体，并且对 G-四链体具有很高的选择性，超过了双链 DNA。构效关系（SAR）研究表明，喹唑啉的二取代和酰胺侧链的长度对于其与 G-四链体的相互作用很重要。此外，还研究了喹唑啉衍生物对端粒酶的抑制作用及其细胞效应。
