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

被引：43

作者：

Basiri, Alireza ^{[1
]}

Murugaiyah, Vikneswaran ^{[1
]}

Osman, Hasnah ^{[2
]}

Kumar, Raju Suresh ^{[3
]}

Kia, Yalda ^{[2
]}

Awang, Khalijah Binti ^{[4
]}

Ali, Mohamed Ashraf ^{[5
]}

机构：

[1] Univ Sains Malaysia, Sch Pharmaceut Sci, Minden 11800, Penang, Malaysia

[2] Univ Sains Malaysia, Sch Chem Sci, Minden 11800, Penang, Malaysia

[3] King Saud Univ, Coll Sci, Dept Chem, Riyadh 11451, Saudi Arabia

[4] Univ Malaya, Fac Sci, Dept Chem, Kuala Lumpur 50603, Malaysia

[5] Univ Sains Malaysia, Inst Res Mol Med, Minden 11800, Penang, Malaysia

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2013年 / 67卷

关键词：

AChE; BChE; Multi-component reaction; Ionic liquid; Molecular modeling; ALZHEIMERS-DISEASE; ACETYLCHOLINESTERASE INHIBITORS; BUTYRYLCHOLINESTERASE; BINDING; SUBSTRATE; DOCKING; DESIGN; AGENTS;

D O I：

10.1016/j.ejmech.2013.06.054

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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. (C) 2013 Elsevier Masson SAS. All rights reserved.

引用

页码：221 / 229

页数：9

共 34 条

[1] Inhibitory effect of curcuminoids on acetylcholinesterase activity and attenuation of scopolamine-induced amnesia may explain medicinal use of turmeric in Alzheimer's disease [J].

Ahmed, Touqeer ;

Gilani, Anwarul-Hassan .

PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR, 2009, 91 (04) :554-559

[2] SUBSTITUTED 1,4-DIHYDROPYRIMIDINES .3. SYNTHESIS OF SELECTIVELY FUNCTIONALIZED 2-HETERO-1,4-DIHYDROPYRIMIDINES [J].

ATWAL, KS ;

ROVNYAK, GC ;

OREILLY, BC ;

SCHWARTZ, J .

JOURNAL OF ORGANIC CHEMISTRY, 1989, 54 (25) :5898-5907

[3] Microwave assisted synthesis, cholinesterase enzymes inhibitory activities and molecular docking studies of new pyridopyrimidine derivatives [J].

Basiri, Alireza ;

Murugaiyah, Vikneswaran ;

Osman, Hasnah ;

Kumar, Raju Suresh ;

Kia, Yalda ;

Ali, Mohamed Ashraf .

BIOORGANIC & MEDICINAL CHEMISTRY, 2013, 21 (11) :3022-3031

[4]

Batsch N., 2012, WORLD ALZHEIMERS REP

[5] Is there a rationale for the use of acetylcholinesterase inhibitors in the therapy of Alzheimer's disease? [J].

Benzi, G ;

Moretti, A .

EUROPEAN JOURNAL OF PHARMACOLOGY, 1998, 346 (01) :1-13

[6] Synthesis and biological activity of analogues of ptilomycalin A [J].

Black, GP ;

Coles, SJ ;

Hizi, A ;

Howard-Jones, AG ;

Hursthouse, MB ;

McGown, AT ;

Loya, S ;

Moore, CG ;

Murphy, PJ ;

Smith, NK ;

Walshe, NDA .

TETRAHEDRON LETTERS, 2001, 42 (19) :3377-3381

[7] Structures of Human Acetylcholinesterase in Complex with Pharmacologically Important Ligands [J].

Cheung, Jonah ;

Rudolph, Michael J. ;

Burshteyn, Fiana ;

Cassidy, Michael S. ;

Gary, Ebony N. ;

Love, James ;

Franklin, Matthew C. ;

Height, Jude J. .

JOURNAL OF MEDICINAL CHEMISTRY, 2012, 55 (22) :10282-10286

[8]

Cokugras AN., 2003, TURK J BIOCHEM, V28, P54, DOI DOI 10.1016/J.CBI.2005.10.013

[9] Treatment options in Alzheimer's disease: Maximizing benefit, managing expectations [J].

Farlow, Martin R. ;

Miller, Michael L. ;

Pejovic, Vojislav .

DEMENTIA AND GERIATRIC COGNITIVE DISORDERS, 2008, 25 (05) :408-422

[10] Facile synthesis of oxo-/thioxopyrimidines and tetrazoles C-C linked to sugars as novel non-toxic antioxidant acetylcholinesterase inhibitors [J].

Figueiredo, J. A. ;

Ismael, M. I. ;

Pinheiro, J. M. ;

Silva, A. M. S. ;

Justino, J. ;

Silva, F. V. M. ;

Goulart, M. ;

Mira, D. ;

Araujo, M. E. M. ;

Campoy, R. ;

Rauter, A. P. .

CARBOHYDRATE RESEARCH, 2012, 347 (01) :47-54

← 1 2 3 4 →