Synthesis, characterization and molecular docking of novel lonazolac analogues 3-(3-hydroxy-5-methyl-1H-pyrazol-4-yl)-3-arylpropanoic acid derivatives: Highly potential COX-1/COX-2, matrix and denaturation inhibitors

被引:8
作者
Pawar, Varsha [1 ]
Shastri, Lokesh A. [1 ]
Gudimani, Parashuram [1 ]
Joshi, Shrinivas [2 ]
Sunagar, Vinay [3 ]
机构
[1] Karnatak Univ, Dept Chem, Dharwad 580003, Karnataka, India
[2] SETs Coll Pharm, Dept Pharmaceut Chem, Novel Drug Design & Discovery Lab, Dharwad 580002, Karnataka, India
[3] GSS Coll, Dept Chem, Belagavi, Karnataka, India
关键词
Prostaglandins; Arachidonic acid; NSAIDs; Lonazolac; Phenybutazone; MMP'S; PYRAZOLONE DERIVATIVES; BIOLOGICAL EVALUATION; ANTIBACTERIAL; MECHANISM;
D O I
10.1016/j.molstruc.2022.132782
中图分类号
O64 [物理化学(理论化学)、化学物理学];
学科分类号
070304 ; 081704 ;
摘要
The present article involves the design, synthesis, characterization, docking studies and anti-inflammatory activity of two new series of lonazolac analogue: 2a-p. Among the synthesized series, compounds 2b, 2c, 2e, 2f, 2 g, 2j, 2k, 2 m, 2n and 2o were screened for their in vitro COX-1 and COX-2 inhibition. All the screened targets exhibited excellent COX-1 and COX-2 inhibitory activity with low IC50 values compared to standard aspirin. Compound 2n showed excellent COX-1 inhibitory activity (IC50 = 127.00 mu l/ml) while compound 2g was an excellent COX-2 inhibitor (IC50 = 5.83 mu l/ml). Both 2n and 2g have superior selective index values of 19.53 and 29.41, respectively. The synthesized compounds 2a-2p, were screened against MMP-2 and MMP-9, anti-inflammatory activity comparable to that of tetracycline, as shown by gelatin zymography. Among the tested compounds, 2l showed excellent anti-inflammatory activity against both MMPs. On the other hand, the protein denaturation technique indicates that most of the molecules are beneficially active. A molecular docking study was performed to rationalize the anti-inflammatory activity of the synthesized compounds against standard celecoxib and aspirin, the results obtained are much better than the standard. (c) 2022 Elsevier B.V. All rights reserved.
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页数:15
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