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

ABSTRACT: 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 t1/2 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.

SUBMITTER: Singh P

PROVIDER: S-EPMC6030096 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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

Singh Palwinder P Kaur Jagroop J Kaur Harpreet H Kaur Anudeep A Bhatti Rajbir R

Scientific reports 20180703 1

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 t1/2 7.5 h. ...[more]

PMID: 29968808

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Dataset Information

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

Publications

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

Similar Datasets

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