Synergy of Physico-chemical and Biological Experiments for Developing a Cyclooxygenase-2 Inhibitor

被引：12

作者：

Singh, Palwinder ^{[1
]}

Kaur, Jagroop ^{[1
]}

Kaur, Harpreet ^{[1
]}

Kaur, Anudeep ^{[2
]}

Bhatti, Rajbir ^{[2
]}

机构：

[1] Guru Nanak Dev Univ, Dept Chem, Ctr Adv Studies, Amritsar 143005, Punjab, India

[2] Guru Nanak Dev Univ, Dept Pharmaceut Sci, Amritsar 143005, Punjab, India

来源：

SCIENTIFIC REPORTS | 2018年 / 8卷

关键词：

NONSTEROIDAL ANTIINFLAMMATORY DRUGS; NSAIDS; CYCLO-OXYGENASE-2; PREDICTION; MOLECULES; PEPTIDES; DESIGN; RISK;

D O I：

10.1038/s41598-018-28408-8

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The physiological consequences of COX-2 overexpression in the development of cancer, diabetes and neurodegenerative diseases have made this enzyme a promising therapeutic target. Herein, COX-2 active site was analyzed and new molecules were designed. We identified a highly potent molecule (S)-3a with IC50 value and the selectivity for COX-2 0.6 nM and 1666, respectively. The MTD of (S)-3a was 2000 mg kg(-1) and its pharmacokinetic studies in rat showed t(1/2) 7.5 h. This compound reversed acetic acid induced analgesia and carragennan induced inflammation by 50% and 25% in rat when used at a dose 10 mg kg(-1). Mechanistically, it was found that compound (S)-3a inhibits COX-2. Overall, the combination of physico-chemical and biological experiments facilitated the development of a new lead molecule to anti-inflammatory drug.

引用

页数：14

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