1437709-07-3Relevant academic research and scientific papers
Design and synthesis of new piperidone grafted acetylcholinesterase inhibitors
Basiri, Alireza,Xiao, Michelle,McCarthy, Alec,Dutta, Debashis,Byrareddy, Siddappa N.,Conda-Sheridan, Martin
, p. 228 - 231 (2017)
Alzheimer's disease (AD) is a neurodegenerative disorder affecting 35?million people worldwide. A common strategy to improve the well-being of AD patients consists on the inhibition of acetylcholinesterase with the concomitant increase of the neurotransmitter acetylcholine at cholinergic synapses. Two series of unreported N-benzylpiperidines 5(a–h) and thiazolopyrimidines 9(a–q) molecules were synthesized and evaluated in vitro for their acetylcholinesterase (AChE) inhibitory activities. Among the newly synthesized compounds, 5h, 9h, 9j, and 9p displayed higher AChE enzyme inhibitory activities than the standard drug, galantamine, with IC50values of 0.83, 0.98, and 0.73?μM, respectively. Cytotoxicity studies of 5h, 9h, 9j, 9n and 9p on human neuroblastoma cells SH-SY5Y, showed no toxicity up to 40?μM concentration. Molecular docking simulations of the active compounds 5h and 9p disclosed the crucial role of π-π-stacking in their binding interaction to the active site AChE enzyme. The presented compounds have potential as AChE inhibitors and potential AD drugs.
Microwave assisted synthesis, cholinesterase enzymes inhibitory activities and molecular docking studies of new pyridopyrimidine derivatives
Basiri, Alireza,Murugaiyah, Vikneswaran,Osman, Hasnah,Kumar, Raju Suresh,Kia, Yalda,Ali, Mohamed Ashraf
, p. 3022 - 3031 (2013/07/04)
A series of hitherto unreported pyrido-pyrimidine-2-ones/pyrimidine-2- thiones were synthesized under microwave assisted solvent free reaction conditions in excellent yields and evaluated in vitro for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes inhibitory activity. Among the pyridopyrimidine derivatives, 7e and 7l displayed 2.5- and 1.5-fold higher enzyme inhibitory activities against AChE as compared to standard drug, galanthamine, with IC50 of 0.80 and 1.37 μM, respectively. Interestingly, all the compounds except 6k, 7j and 7k displayed higher inhibitory potential against BChE enzyme in comparison to standard with IC50 ranging from 1.18 to 18.90 μM. Molecular modeling simulations of 7e and 7l was performed using three-dimensional structure of Torpedo californica AChE (TcAChE) and human butyrylcholinesterase (hBChE) enzymes to disclose binding interaction and orientation of these molecule into the active site gorge of respective receptors.
