Department of Organic Chemistry, Faculty of Chemistry, University of Lodz, Tamka 12, 91-403 Lodz, Poland.
ICGM, Univ. Montpellier, CNRS, ENSCM, 34090 Montpellier, France.
Int J Mol Sci. 2022 Jul 22;23(15):8091. doi: 10.3390/ijms23158091.
The quest to find new inhibitors of biologically relevant targets is considered an important strategy to introduce new drug candidates for the treatment of neurodegenerative diseases. A series of (aminomethyl)benzylphosphonates - and their metallocarbonyl iron - and ruthenium - complexes were designed, synthesized, and evaluated for their inhibitory potentials against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) by determination of IC. Metallocarbonyl derivatives, in general, did not show significant inhibition activity against these enzymes, the most potent inhibitor was the (aminomethyl)benzylphosphonate (IC = 1.215 µM against AChE). Molecular docking analysis of AChE and (aminomethyl)benzylphosphonates - showed the strongest interactions of and AChE compared to isomers and . Cytotoxicity studies of synthesized compounds towards the V79 cell line were also performed and discussed.
寻找新的生物相关靶标抑制剂被认为是引入治疗神经退行性疾病的新药物候选物的重要策略。设计、合成了一系列（氨甲基）苄基膦酸酯-及其金属羰基铁-和钌-配合物，并通过测定 IC 来评估它们对乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BuChE）的抑制潜力。一般来说，金属羰基衍生物对这些酶没有显示出显著的抑制活性，最有效的抑制剂是（氨甲基）苄基膦酸酯（对 AChE 的 IC = 1.215µM）。AChE 和（氨甲基）苄基膦酸酯的分子对接分析表明，与异构体和相比，和与 AChE 具有最强的相互作用。还对合成化合物对 V79 细胞系的细胞毒性进行了研究和讨论。
