New quinazoline derivatives for telomeric G-quadruplex DNA: Effects of an added phenyl group on quadruplex binding ability

To improve the selectivity of indoloquinoline or benzofuroquinoline derivatives, we previously reported several quinazoline derivatives [17]. These compounds could mimic a tetracyclic aromatic system through intramolecular hydrogen bond. Studies showed that these quinazoline derivatives were effective and selective telomeric G-quadruplex ligands. With this encouragement, here we synthesized a series of N-(2-(quinazolin-2-yl)phenyl)benzamide (QPB) compounds as modified quinazoline derivatives. In this modification, a phenyl group was introduced to the aromatic core. The evaluation results showed that part of QPB derivatives had stronger binding ability and better selectivity for telomeric G-quadruplex DNA than LZ-11, the most potential compound of reported quinazoline derivatives. Furthermore, telomerase inhibition of QPB derivatives and their cellular effects were studied.

Graphical abstractA series of compounds with an introduction of phenyl group to previous reported quinazoline derivatives were synthesized and evaluated. These compounds showed enhanced telomeric G-quadruplex DNA binding activity and selectivity .Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Compounds with an introduction of phenyl group to quinazoline derivatives were synthesized. ► Compounds showed enhanced binding affinity and selectivity for telomeric G-quadruplex DNA. ► 15e could significantly inhibit cellular biological activity.