Spiropyrrolidine/spiroindolizino[6,7-b]indole heterocyclic hybrids: Stereoselective synthesis, cholinesterase inhibitory activity and their molecular docking study

被引：40

作者：

Arumugam, Natarajan ^{[1
]}

Almansour, Abdulrahman I. ^{[1
]}

Kumar, Raju Suresh ^{[1
]}

Altaf, Mohammad ^{[1
,2
]}

Padmanaban, R. ^{[3
]}

Sureshbabu, Popuri ^{[3
]}

Angamuthu, Gnanavel ^{[3
]}

Kotresha, D. ^{[4
]}

Manohar, Thota Sai ^{[5
]}

Venketesh, S. ^{[5
]}

机构：

[1] King Saud Univ, Coll Sci, Dept Chem, POB 2455, Riyadh 11451, Saudi Arabia

[2] King Saud Univ, Coll Sci, Cent Lab, POB 2455, Riyadh 11451, Saudi Arabia

[3] Pondicherry Univ, Sch Phys Chem & Appl Sci, Dept Chem, Kalapet 605014, Puducherry, India

[4] East West Grp Inst, Dept Microbiol, 63 Anjananagar, Bangaluru 560091, Karnataka, India

[5] Sri Sathya Sai Inst Higher Learning, Dept Biosci, Prasanthinilayam 515134, AP, India

来源：

BIOORGANIC CHEMISTRY | 2018年 / 79卷

关键词：

Spiropyrrolidines; Spiroindolizinoindoles; 1,3-Dipolar cycloaddition reaction; Alzheimer disease; AChE and BChE inhibitors; Docking studies; ALZHEIMERS-DISEASE;

D O I：

10.1016/j.bioorg.2018.04.025

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A regio and stereo- selective synthesis of hitherto unexplored hybrid heterocyclic system comprising spiropyrrolidine, indolizino[6,7-b]indole units in good to excellent yields, has been developed via three component 1,3-dipolar cycloaddition and concomitant trifluoroacetic acid catalyzed Pictet-Spengler cyclization with paraformaldehyde. The newly synthesized compounds were evaluated for their in vitro acetylcholinesterase (AChE) and butylcholinesterase (BChE) enzyme inhibitory activities. Most of the synthesized compounds showed good inhibitory activity, among them, compounds 4d and 4g displayed highest potency against AChE (IC50 1.88 and 1.98 mu M), and BChE (IC50 18.32 and 10.21 mu M) enzyme, respectively than the standard drug, galanthamine. Molecular modeling simulation was investigated for the most active compounds 4d and 4g on AChE and BChE enzymes to disclose the binding and orientation of these molecules into active site of respective receptors.

引用

页码：64 / 71

页数：8

共 17 条

[1] A Facile Ionic Liquid Promoted Synthesis, Cholinesterase Inhibitory Activity and Molecular Modeling Study of Novel Highly Functionalized Spiropyrrolidines [J].

Almansour, Abdulrahman I. ;

Kumar, Raju Suresh ;

Arumugam, Natarajan ;

Basiri, Alireza ;

Kia, Yalda ;

Ali, Mohamed Ashraf ;

Farooq, Mehvish ;

Murugaiyah, Vikneswaran .

MOLECULES, 2015, 20 (02) :2296-2309

[2]

Alzheimer's Disease International, 2009, ALZH DIS INT WORLD A

[3] Synthesis and cholinesterase inhibitory activity study of new piperidone grafted spiropyrrolidines [J].

Basiri, Alireza ;

Abd Razik, Basma M. ;

Ezzat, Mohammed Oday ;

Kia, Yalda ;

Kumar, Raju Suresh ;

Almansour, Abdulrahman I. ;

Arumugam, Natarajan ;

Murugaiyah, Vikneswaran .

BIOORGANIC CHEMISTRY, 2017, 75 :210-216

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

Basiri, Alireza ;

Murugaiyah, Vikneswaran ;

Osman, Hasnah ;

Kumar, Raju Suresh ;

Kia, Yalda ;

Awang, Khalijah Binti ;

Ali, Mohamed Ashraf .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2013, 67 :221-229

[5] Disease-modifying therapies for Alzheimer disease [J].

Cummings, Jeffrey L. ;

Doody, Rachelle ;

Clark, Christopher .

NEUROLOGY, 2007, 69 (16) :1622-1634

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

Giacobini, E .

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

[7] A century of Alzheimer's disease [J].

Goedert, Michel ;

Spillantini, Maria Grazia .

SCIENCE, 2006, 314 (5800) :777-781

[8] Ionic liquid mediated synthesis of mono- and bis-spirooxindole-hexahydropyrrolidines as cholinesterase inhibitors and their molecular docking studies [J].

Kia, Yalda ;

Osman, Hasnah ;

Kumar, Raju Suresh ;

Basiri, Alireza ;

Murugaiyah, Vikneswaran .

BIOORGANIC & MEDICINAL CHEMISTRY, 2014, 22 (04) :1318-1328

[9] A facile chemo-, regio- and stereoselective synthesis and cholinesterase inhibitory activity of spirooxindole-pyrrolizine-piperidine hybrids [J].

Kia, Yalda ;

Osman, Hasnah ;

Kumar, Raju Suresh ;

Murugaiyah, Vikneswaran ;

Basiri, Alireza ;

Perumal, Subbu ;

Razak, Ibrahim Abdul .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2013, 23 (10) :2979-2983

[10] Synthesis and discovery of novel piperidone-grafted mono- and bis-spirooxindole-hexahydropyrrolizines as potent cholinesterase inhibitors [J].

Kia, Yalda ;

Osman, Hasnah ;

Kumar, Raju Suresh ;

Murugaiyah, Vikneswaran ;

Basiri, Alireza ;

Perumal, Subbu ;

Wahab, Habibah A. ;

Bing, Choi Sy .

BIOORGANIC & MEDICINAL CHEMISTRY, 2013, 21 (07) :1696-1707

← 1 2 →