2. Academic Validation
  3. Novel 4-aminoquinoline analogs targeting the HIF-1α signaling pathway

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

  • Future Med Chem. 2023 Sep;15(17):1569-1582. doi: 10.4155/fmc-2023-0169.
Yu-Chieh Wu 1,  Meng-Tien Lu 2 3,  Po-Chen Chu 2 3,  Chih-Shiang Chang 1 3
Affiliations

Affiliations

  • 1 School of Pharmacy, College of Pharmacy, China Medical University, Taichung, 40604, Taiwan.
  • 2 Department of Cosmeceutics & Graduate Institute of Cosmeceutics, China Medical University, Taichung, 40604, Taiwan.
  • 3 Drug Development Center, China Medical University, Taichung, 40604, Taiwan.
PMID: 37728024 DOI: 10.4155/fmc-2023-0169
Abstract

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 4-aminoquinoline scaffold in the development of Anticancer agents by targeting the HIF-1α 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-1α signaling pathway. Conclusion: Compound 3s was identified as the most promising HIF-1α inhibitor due to its exceptional antiproliferative effects, with IC50 values of 0.6 and 53.3 nM observed in MiaPaCa-2 and MDA-MB-231 cells, respectively. Furthermore, compound 3s was found to inhibit HIF-1α expression by decreasing the level of HIF-1α mRNA.

Keywords

4-aminoquinoline; anticancer; hypoxia-inducible factor-1α.

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