Novel 4-aminoquinoline analogs targeting the HIF-1α signaling pathway.

The aminoquinoline core exhibits versatile pharmacological properties, particularly in the area of anticancer activity. This study was designed to investigate the potential of the 4-aminoquinoline scaffold in the development of anticancer agents by targeting the HIF-1α signaling pathway. The authors synthesized multiple derivatives of 4-aminoquinoline containing heterocyclic rings by a microwave reactor and assessed the cytotoxicity and inhibitory effects of these derivatives on the HIF-1α signaling pathway. Compound was identified as the most promising HIF-1α inhibitor due to its exceptional antiproliferative effects, with IC values of 0.6 and 53.3 nM observed in MiaPaCa-2 and MDA-MB-231 cells, respectively. Furthermore, compound was found to inhibit HIF-1α expression by decreasing the level of HIF-1α mRNA.