Suwanhom Paptawan, Nualnoi Teerapat, Khongkow Pasarat, Tipmanee Varomyalin, Lomlim Luelak
Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand.
Phytomedicine and Pharmaceutical Biotechnology Excellent Center (PPBEC), Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand.
ACS Omega. 2023 Aug 29;8(36):32498-32511. doi: 10.1021/acsomega.3c02683. eCollection 2023 Sep 12.
A new family of lawsone-quinoxaline hybrids was designed, synthesized, and evaluated as dual binding site cholinesterase inhibitors (ChEIs). tests revealed that compound was the most potent AChEI (IC = 20 nM) and BChEI (IC = 220 nM). The compound did not show cytotoxicity against the SH-SY5Y neuronal cells (GI > 100 μM). and enzyme kinetic experiments demonstrated that compound bound to both the catalytic anionic site and the peripheral anionic site of AChE. The lawsone-quinoxaline hybrids exhibited potential for further development of potent acetylcholinesterase inhibitors for the treatment of Alzheimer's disease.
设计、合成并评估了一类新型的劳森酮-喹喔啉杂化物作为双结合位点胆碱酯酶抑制剂（ChEIs）。测试表明化合物是最有效的乙酰胆碱酯酶抑制剂（IC = 20 nM）和丁酰胆碱酯酶抑制剂（IC = 220 nM）。该化合物对SH-SY5Y神经细胞未显示出细胞毒性（GI > 100 μM）。酶动力学实验表明化合物与乙酰胆碱酯酶的催化阴离子位点和外周阴离子位点均有结合。劳森酮-喹喔啉杂化物展现出进一步开发用于治疗阿尔茨海默病的强效乙酰胆碱酯酶抑制剂的潜力。
