Shokouhi Asl Amir Shervin, Sayahi Mohammad Hosein, Hashempur Mohammad Hashem, Irajie Cambyz, Alaeddini Amir Hossein, Ghafouri Seyedeh Niloufar, Noori Milad, Dastyafteh Navid, Mottaghipisheh Javad, Asadi Mehdi, Larijani Bagher, Mahdavi Mohammad, Iraji Aida
Department of Medicinal Chemistry, School of Pharmacy, Iran University of Medical Sciences, Tehran, Iran.
Department of Chemistry, Payame Noor University, Tehran, Iran.
Sci Rep. 2025 Jan 3;15(1):655. doi: 10.1038/s41598-024-83020-3.
In this study, new cinnamic acid linked to triazole acetamide derivatives was synthesized and evaluated for anti-Alzheimer and anti-melanogenesis activities. The structural elucidation of all analogs was performed using different analytical techniques, including H-NMR, C-NMR, mass spectrometry, and IR spectroscopy. The synthesized compounds were assessed in vitro for their inhibitory activities against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and tyrosinase enzymes. Among synthesize derivative compound 3-(4-((1-(2-((2,4-dichlorophenyl)amino)-2-oxoethyl)-1H-1,2,3-triazol-4-yl)methoxy)-3-methoxyphenyl)acrylic acid (10j) exhibited the highest activity against BChE with an IC value of 11.99 ± 0.53 µM. Derivative 3-(3-methoxy-4-((1-(2-oxo-2-(p-tolylamino)ethyl)-1H-1,2,3-triazol-4-yl)methoxy)phenyl)acrylic acid (10d), bearing a 4-CH group, was identified as the most potent AChE inhibitor. In terms of tyrosinase inhibition, 3-(3-methoxy-4-((1-(2-((2-methyl-4-nitrophenyl)amino)-2-oxoethyl)-1H-1,2,3-triazol-4-yl)methoxy)phenyl)acrylic acid (compound 10n), demonstrated 44.87% inhibition at a concentration of 40 µM. Additionally, a kinetic study of compound 10j which 2,4-dichlorophenyl substituents against BChE revealed a mixed-type inhibition pattern. Furthermore, molecular docking and molecular dynamic studies of compound 10j were conducted to thoroughly evaluate its mode of action within the BChE active site.
在本研究中，合成了与三唑乙酰胺衍生物相连的新型肉桂酸，并对其抗阿尔茨海默病和抗黑色素生成活性进行了评估。使用不同的分析技术对所有类似物进行结构解析，包括氢核磁共振（H-NMR）、碳核磁共振（C-NMR）、质谱和红外光谱。对合成的化合物进行体外评估，以检测它们对乙酰胆碱酯酶（AChE）、丁酰胆碱酯酶（BChE）和酪氨酸酶的抑制活性。在合成的衍生物中，化合物3-(4-((1-(2-((2,4-二氯苯基)氨基)-2-氧代乙基)-1H-1,2,3-三唑-4-基)甲氧基)-3-甲氧基苯基)丙烯酸（10j）对BChE表现出最高活性，IC值为11.99±0.53µM。带有4-CH基团的衍生物3-(3-甲氧基-4-((1-(2-氧代-2-(对甲苯基氨基)乙基)-1H-1,2,3-三唑-4-基)甲氧基)phenyl)丙烯酸（10d）被确定为最有效的AChE抑制剂。在酪氨酸酶抑制方面，化合物3-(3-甲氧基-4-((1-(2-((2-甲基-4-硝基苯基)氨基)-2-氧代乙基)-1H-1,2,3-三唑-4-基)甲氧基)phenyl)丙烯酸（化合物10n）在浓度为40µM时表现出44.87%的抑制率。此外，对具有2,4-二氯苯基取代基的化合物10j针对BChE的动力学研究揭示了一种混合型抑制模式。此外，还对化合物10j进行了分子对接和分子动力学研究，以全面评估其在BChE活性位点内的作用模式。
