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.

A 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 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.