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

Background: The aminoquinoline core exhibits versatile pharmacological properties, particularly in the area of anticancer activity. This study was designed to investigate the potential of the 4aminoquinoline scaffold in the development of anticancer agents by targeting the HIF-1 alpha signaling pathway. Methodology: 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-1 alpha signaling pathway. Conclusion: Compound 3s was identified as the most promising HIF-1 alpha inhibitor due to its exceptional antiproliferative effects, with IC50 values of 0.6 and 53.3 nMobserved inMiaPaCa-2 and MDA-MB-231 cells, respectively. Furthermore, compound 3s was found to inhibit HIF-1 alpha expression by decreasing the level of HIF-1 alpha mRNA.