Wu Yu-Chieh, Lu Meng-Tien, Chu Po-Chen, Chang Chih-Shiang
School of Pharmacy, College of Pharmacy, China Medical University, Taichung, 40604, Taiwan.
Department of Cosmeceutics & Graduate Institute of Cosmeceutics, China Medical University, Taichung, 40604, Taiwan.
Future Med Chem. 2023 Sep;15(17):1569-1582. doi: 10.4155/fmc-2023-0169. Epub 2023 Sep 20.
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.
氨基喹啉核心具有多种药理特性，尤其是在抗癌活性领域。本研究旨在通过靶向缺氧诱导因子-1α（HIF-1α）信号通路，探讨4-氨基喹啉骨架在抗癌药物开发中的潜力。作者通过微波反应器合成了多种含杂环的4-氨基喹啉衍生物，并评估了这些衍生物对HIF-1α信号通路的细胞毒性和抑制作用。化合物被确定为最有前景的HIF-1α抑制剂，因为它具有特殊的抗增殖作用，在MiaPaCa-2和MDA-MB-231细胞中观察到的半数抑制浓度（IC）值分别为0.6和53.3 nM。此外，发现化合物通过降低HIF-1α mRNA水平来抑制HIF-1α表达。
