A facile chemo-, regio- and stereoselective synthesis and cholinesterase inhibitory activity of spirooxindole-pyrrolizine-piperidine hybrids

被引：69

作者：

Kia, Yalda ^{[1
]}

Osman, Hasnah ^{[1
]}

Kumar, Raju Suresh ^{[2
]}

Murugaiyah, Vikneswaran ^{[3
]}

Basiri, Alireza ^{[3
]}

Perumal, Subbu ^{[4
]}

Razak, Ibrahim Abdul ^{[5
]}

机构：

[1] Univ Sains Malaysia, Sch Chem Sci, Usm 11800, Penang, Malaysia

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

[3] Univ Sains Malaysia, Sch Pharmaceut Sci, Usm 11800, Penang, Malaysia

[4] Madurai Kamaraj Univ, Sch Chem, Dept Organ Chem, Madurai 625021, Tamil Nadu, India

[5] Univ Sains Malaysia, Sch Phys, Usm 11800, Penang, Malaysia

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2013年 / 23卷 / 10期

关键词：

AChE; BChE; 1,3-Dipolar cycloaddition; Selectivity and spiropyrrolizines; ALZHEIMERS-DISEASE; ACETYLCHOLINESTERASE INHIBITORS; SITE GORGE; BUTYRYLCHOLINESTERASE; DERIVATIVES; SUBSTRATE; BINDING; BRAIN; PHASE;

D O I：

10.1016/j.bmcl.2013.03.027

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of novel hybrid spiro heterocycles comprising pyrrolizine, spiroxindole and piperidine moieties was synthesized chemo-, regio- and stereoselectively in good yields from 1,3-dipolar cycloaddition reaction of a series of 1-acryloyl-3,5-bisarylmethylidenepiperidin-4-ones with azomethine ylides generated in situ from 5-choloroisatin and L-proline in methanol. These cycloadducts displayed significant cholinesterase inhibitory activity. Among the compounds screened, 8g and 8e, showed maximum inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinestrase (BChE) with IC50 values of 3.33 and 3.13 mu M, respectively. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：2979 / 2983

页数：5

共 29 条

[1] Design, synthesis, in vitro evaluation of tetrahydropyrimidine-isatin hybrids as potential antibacterial, antifungal and anti-tubercular agents [J].

Akhaja, Tarunkumar Nanjibhai ;

Raval, Jignesh Priyakant .

CHINESE CHEMICAL LETTERS, 2012, 23 (04) :446-449

[2]

AXELSEN PH, 1994, PROTEIN SCI, V3, P188

[3] (3E,5E)-1-Acryloyl-3,5-bis(2-chlorobenzylidene)piperidin-4-one [J].

Basiri, Alireza ;

Murugaiyah, Vikneswaran ;

Osman, Hasnah ;

Hemamalini, Madhukar ;

Fun, Hoong-Kun .

ACTA CRYSTALLOGRAPHICA SECTION E-STRUCTURE REPORTS ONLINE, 2011, 67 :O1228-U1390

[4]

Cordell G.A., 1998, The Alkaloids: Chemistry and Biology

[5] Novel mammalian cell cycle inhibitors, spirotryprostatins A and B, produced by Aspergillus fumigatus, which inhibit mammalian cell cycle at G2/M phase [J].

Cui, CB ;

Kakeya, H ;

Osada, H .

TETRAHEDRON, 1996, 52 (39) :12651-12666

[6] A conformational and structure-activity relationship study of cytotoxic 3,5-bis(arylidene)-4-piperidones and related N-acryloyl analogues [J].

Dimmock, JR ;

Padmanilayam, MP ;

Puthucode, RN ;

Nazarali, AJ ;

Motaganahalli, NL ;

Zello, GA ;

Quail, JW ;

Oloo, EO ;

Kraatz, HB ;

Prisciak, JS ;

Allen, TM ;

Santos, CL ;

Balzarini, J ;

De Clercq, E ;

Manavathu, EK .

JOURNAL OF MEDICINAL CHEMISTRY, 2001, 44 (04) :586-593

[7] Cholinesterase inhibitors for Alzheimer's disease therapy: from tacrine to future applications [J].

Giacobini, E .

NEUROCHEMISTRY INTERNATIONAL, 1998, 32 (5-6) :413-419

[8] Comparison of the antiplasmodial and falcipain-2 inhibitory activity of β-amino alcohol thiolactone-chalcone and isatin-chalcone hybrids [J].

Hans, Renate H. ;

Gut, Jiri ;

Rosenthal, Philip J. ;

Chibale, Kelly .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2010, 20 (07) :2234-2237

[9] The X-ray structure of a transition state analog complex reveals the molecular origins of the catalytic power and substrate specificity of acetylcholinesterase [J].

Harel, M ;

Quinn, DM ;

Nair, HK ;

Silman, I ;

Sussman, JL .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1996, 118 (10) :2340-2346

[10] QUATERNARY LIGAND-BINDING TO AROMATIC RESIDUES IN THE ACTIVE-SITE GORGE OF ACETYLCHOLINESTERASE [J].

HAREL, M ;

SCHALK, I ;

EHRETSABATIER, L ;

BOUET, F ;

GOELDNER, M ;

HIRTH, C ;

AXELSEN, PH ;

SILMAN, I ;

SUSSMAN, JL .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (19) :9031-9035

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