An expedient, ionic liquid mediated multi-component synthesis of novel piperidone grafted cholinesterase enzymes inhibitors and their molecular modeling study

作者：Basiri Alireza; Murugaiyah Vikneswaran^*; Osman Hasnah; Kumar Raju Suresh; Kia Yalda; Awang Khalijah Binti; Ali Mohamed Ashraf

来源：European Journal of Medicinal Chemistry, 2013, 67: 221-229.

DOI：10.1016/j.ejmech.2013.06.054

• AChE
• BChE
• Multi-component reaction
• Ionic liquid
• Molecular modeling

Series of hitherto unreported piperidone grafted pyridopyrimidines synthesized through ionic liquid mediated multi-component reaction. These compounds were evaluated for their inhibitory activities against AChE and BChE enzymes. All the compounds displayed considerable potency against AChE with IC50 values ranging from 0.92 to 9.11 mu M, therein compounds 6a, 6h and 6i displayed superior enzyme inhibitory activities compared to standard drug with IC50 values of 0.92, 1.29 and 2.07 mu M. Remarkably, all the compounds displayed higher BChE inhibitory activity compared to galantamine with IC50 values of 1.89-8.13 mu M. Molecular modeling, performed for the most active compounds using three dimensional crystal structures of TcAChE and hBChE, disclosed binding template of these inhibitors into the active site of their respective enzymes.

• 出版日期2013-9