Synthesis of novel pyrazole-thiadiazole hybrid as potential potent and selective cyclooxygenase-2 (COX-2) inhibitors

被引：43

作者：

Alegaon, S. G. ^{[1
]}

Hirpara, M. B. ^{[1
]}

Alagawadi, K. R. ^{[1
]}

Hullatti, K. K. ^{[2
]}

Kashniyal, K. ^{[1
]}

机构：

[1] KLE Univ, KLES Coll Pharm, Dept Pharmaceut Chem, Belgaum 590010, Karnataka, India

[2] KLE Univ, KLES Coll Pharm, Dept Pharmacognosy, Belgaum 590010, Karnataka, India

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2014年 / 24卷 / 22期

关键词：

Pyrazoles; Thiadiazole; COX-1 and COX-2; Cytotoxicity; Docking; Drug likeness; BIOLOGICAL EVALUATION; MOLECULAR DOCKING; DERIVATIVES; DISCOVERY; DESIGN; SERIES; ACID;

D O I：

10.1016/j.bmcl.2014.08.062

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of 1,3,4-trisubstituted pyrazole derivatives (3a-f), (4a-f), and (5a-f) have been synthesized and evaluated for their cyclooxygenase (COX-1 and COX-2) inhibitory activity. The structures of newly synthesized compounds were characterized by IR, H-1 NMR, and mass spectral analysis. All of the compounds showed good inhibition of COX-2 with IC50 of 1.33-17.5 mu M. Among these derivatives, compound (5c) was the most potent and selective COX-2 inhibitor (IC50 = 1.33 mu M), with a significant selectivity index (SI >60). Molecular docking studies were carried out in order to predict the hypothetical binding mode of these compounds to the COX-2 isoenzyme. The result of present study suggests that pyrazole-thiadiazole hybrid could be an interesting approach for the design of new selective COX-2 inhibitory agents. (C) 2014 Elsevier Ltd. All rights reserved.

引用

页码：5324 / 5329

页数：6

共 32 条

[1]

Alegaon S G, 2014, Drug Res (Stuttg), V64, P553, DOI 10.1055/s-0033-1363976

[2] Synthesis, characterization, and biological evaluation of thiazolidine-2,4-dione derivatives [J].

Alegaon, Shankar G. ;

Alagawadi, Kallanagouda R. ;

Pawar, Sneha M. ;

Vinod, D. ;

Rajput, Udaysingh .

MEDICINAL CHEMISTRY RESEARCH, 2014, 23 (02) :987-994

[3] New thiazolidine-2,4-diones as antimicrobial and cytotoxic agent [J].

Alegaon, Shankar G. ;

Alagawadi, Kallanagouda R. .

MEDICINAL CHEMISTRY RESEARCH, 2012, 21 (10) :3214-3223

[4] Novel imidazo[2,1-b][1,3,4]thiadiazole carrying rhodanine-3-acetic acid as potential antitubercular agents [J].

Alegaon, Shankar G. ;

Alagawadi, Kallanagouda R. ;

Sonkusare, Pranali V. ;

Chaudhary, Sagar M. ;

Dadwe, Dilip H. ;

Shah, Amol S. .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2012, 22 (05) :1917-1921

[5]

Alegaon SG, 2011, LETT DRUG DES DISCOV, V8, P612

[6] Synthesis and biological evaluation of some 5-arylidene-2-(1,3-thiazol-2-ylimino)-1,3-thiazolidin-4-ones as dual anti-inflammatory/antimicrobial agents [J].

Apostolidis, I. ;

Liaras, K. ;

Geronikaki, A. ;

Hadjipavlou-Litina, D. ;

Gavalas, A. ;

Sokovic, M. ;

Glamoclija, J. ;

Ciric, A. .

BIOORGANIC & MEDICINAL CHEMISTRY, 2013, 21 (02) :532-539

[7] Synthesis and biological evaluation of a novel series of pyrazole chalcones as anti-inflammatory, antioxidant and antimicrobial agents [J].

Bandgar, Babasaheb P. ;

Gawande, Shrikant S. ;

Bodade, Ragini G. ;

Gawande, Nalini M. ;

Khobragade, Chandrahasya N. .

BIOORGANIC & MEDICINAL CHEMISTRY, 2009, 17 (24) :8168-8173

[8] Synthesis of novel celecoxib analogues by bioisosteric replacement of sulfonamide as potent anti-inflammatory agents and cyclooxygenase inhibitors [J].

Chandna, Nisha ;

Kumar, Satish ;

Kaushik, Pawan ;

Kaushik, Dhirender ;

Roy, Somendu K. ;

Gupta, Girish K. ;

Jachak, Sanjay M. ;

Kapoor, Jitander K. ;

Sharma, Pawan K. .

BIOORGANIC & MEDICINAL CHEMISTRY, 2013, 21 (15) :4581-4590

[9] Cyclooxygenase inhibitors - current status and future prospects [J].

Dannhardt, G ;

Kiefer, W .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2001, 36 (02) :109-126

[10] Synthesis, biological evaluation and molecular modeling study of pyrazole and pyrazoline derivatives as selective COX-2 inhibitors and anti-inflammatory agents. Part 2 [J].

El-Sayed, Magda A. -A. ;

Abdel-Aziz, Naglaa I. ;

Abdel-Aziz, Alaa A. -M. ;

El-Azab, Adel S. ;

ElTahir, Kamal E. H. .

BIOORGANIC & MEDICINAL CHEMISTRY, 2012, 20 (10) :3306-3316

← 1 2 3 4 →