Design, synthesis and biological evaluation of 5-benzylidene-2-iminothiazolidin-4-ones as selective GSK-3β inhibitors

被引：43

作者：

Arfeen, Minhajul ^{[1
]}

Bhagat, Shweta ^{[1
]}

Patel, Rahul ^{[1
]}

Prasad, Shivcharan ^{[2
]}

Roy, Ipsita ^{[2
]}

Chakraborti, Asit K. ^{[1
]}

Bharatam, Prasad V. ^{[1
]}

机构：

[1] Natl Inst Pharmaceut Educ & Res, Dept Med Chem, Sect 67, Sas Nagar 160062, Punjab, India

[2] Natl Inst Pharmaceut Educ & Res, Dept Biotechnol, Sect 67, Sas Nagar 160062, Punjab, India

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2016年 / 121卷

关键词：

GSK-3; CDK-2; Molecular docking; Molecular dynamics; SBDD; SYNTHASE KINASE-3 INHIBITORS; POTENT; DERIVATIVES; DISCOVERY; DISEASE;

D O I：

10.1016/j.ejmech.2016.04.075

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

In this work, iminothiazolidin-4-one derivatives were explored as selective GSK-3 beta inhibitors. Molecular docking analysis was carried to design a series of compounds, which were synthesized using substituted thiourea, 2-bromoacetophenones and benzaldehydes. Out of the twenty five compounds synthesized during this work, the in vitro evaluation against GSK-3 led to the identification of nine compounds with activity in lower nano-molar range (2-85 nM). Further, in vitro evaluation against CDK-2 showed five compounds to be selective towards GSK-3. (C) 2016 Elsevier Masson SAS. All rights reserved.

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收藏

页码：727 / 736

页数：10

相关论文

共 24 条

[1] Molecular design and synthesis of HCV inhibitors based on thiazolone scaffold [J].

Al-Ansary, Ghada H. ;

Ismail, Mohamed A. H. ;

Abou El Ella, Dalal A. ;

Eid, Sameh ;

Abouzid, Khaled A. M. .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2013, 68 :19-32

[2] Molecular dynamics simulation studies of GSK-3β ATP competitive inhibitors: understanding the factors contributing to selectivity [J].

Arfeen, Minhajul ;

Patel, Rahul ;

Khan, Tosif ;

Bharatam, Prasad V. .

JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, 2015, 33 (12) :2578-2593

[3] Design of Glycogen Synthase Kinase-3 Inhibitors: An Overview on Recent Advancements [J].

Arfeen, Minhajul ;

Bharatam, Prasad V. .

CURRENT PHARMACEUTICAL DESIGN, 2013, 19 (26) :4755-4775

[4] Discovery of Novel Potent and Highly Selective Glycogen Synthase Kinase-3β (GSK3β) Inhibitors for Alzheimer's Disease: Design, Synthesis, and Characterization of Pyrazines [J].

Berg, Stefan ;

Bergh, Margareta ;

Hellberg, Sven ;

Hogdin, Katharina ;

Lo-Alfredsson, Yvonne ;

Soderman, Peter ;

von Berg, Stefan ;

Weigelt, Tatjana ;

Ormo, Mats ;

Xue, Yafeng ;

Tucker, Julie ;

Neelissen, Jan ;

Jerning, Eva ;

Nilsson, Yvonne ;

Bhat, Ratan .

JOURNAL OF MEDICINAL CHEMISTRY, 2012, 55 (21) :9107-9119

[5] Structural characterization of the GSK-3β active site using selective and non-selective ATP-mimetic inhibitors [J].

Bertrand, JA ;

Thieffine, S ;

Vulpetti, A ;

Cristiani, C ;

Valsasina, B ;

Knapp, S ;

Kalisz, HM ;

Flocco, M .

JOURNAL OF MOLECULAR BIOLOGY, 2003, 333 (02) :393-407

[6] Structural insights and biological effects of glycogen synthase kinase 3-specific inhibitor AR-A014418 [J].

Bhat, R ;

Xue, YF ;

Berg, S ;

Hellberg, S ;

Ormö, M ;

Nilsson, Y ;

Radesäter, AC ;

Jerning, E ;

Markgren, PO ;

Borgegård, T ;

Nylöf, M ;

Giménez-Cassina, A ;

Hernández, F ;

Lucas, JJ ;

Díaz-Nido, J ;

Avila, J .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (46) :45937-45945

[7] 2-Imino-thiazolidin-4-one Derivatives as Potent, Orally Active S1P1 Receptor Agonists [J].

Bolli, Martin H. ;

Abele, Stefan ;

Binkert, Christoph ;

Bravo, Roberto ;

Buchmann, Stephan ;

Bur, Daniel ;

Gatfield, John ;

Hess, Patrick ;

Kohl, Christopher ;

Mangold, Celine ;

Mathys, Boris ;

Menyhart, Katalin ;

Mueller, Claus ;

Nayler, Oliver ;

Scherz, Michael ;

Schmidt, Gunther ;

Sippel, Virginie ;

Steiner, Beat ;

Strasser, Daniel ;

Treiber, Alexander ;

Weller, Thomas .

JOURNAL OF MEDICINAL CHEMISTRY, 2010, 53 (10) :4198-4211

[8]

Coulibaly Wacothon Karime, 2012, Sci Pharm, V80, P825, DOI 10.3797/scipharm.1206-04

[9] Fragment-based design, docking, synthesis, biological evaluation and structure-activity relationships of 2-benzo/benzisothiazolimino-5-aryliden-4-thiazolidinones as cycloxygenase/lipoxygenase inhibitors [J].

Eleftheriou, Phaedra ;

Geronikaki, Athina ;

Hadjipavlou-Litina, Dimitra ;

Vicini, Paola ;

Tarasova, Olga A. ;

Filimonov, Dmitry ;

Poroikov, Vladimir ;

Chaudhaery, Shailendra S. ;

Roy, Kuldeep K. ;

Saxena, Anil K. .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2012, 47 :111-124

[10] CDK versus GSK-3 inhibition: a purple haze no longer? [J].

Fischer, PM .

CHEMISTRY & BIOLOGY, 2003, 10 (12) :1144-1146