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Tropical Journal of Pharmaceutical Research
Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, Nigeria
ISSN: 1596-5996 EISSN: 1596-5996
Vol. 16, No. 2, 2017, pp. 327-336
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Bioline Code: pr17043
Full paper language: English
Document type: Research Article
Document available free of charge
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Tropical Journal of Pharmaceutical Research, Vol. 16, No. 2, 2017, pp. 327-336
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Pharmacological evaluation of novel dimers of an arylpropionic acid class of non-selective cyclooxygenase inhibitors
Halimi, Syed Muhammad Ashhad; Saeed, Muhammad; Safiullah & Khan, Khalid Muhammed
Abstract
Purpose: To explore and identify cyclooxygenase (COX) inhibitors with optimal potency and efficacy
using an arylpropionic acid class of drugs as lead molecules.
Methods: The selected lead molecules were dimerised through chemical processes (reflux
condensation) and characterised in terms of structural properties using infrared, proton nuclear
magnetic resonance, electron impact mass spectrometry, and elemental analysis techniques. The
molecules were evaluated pharmacologically for acute toxicity and anti-inflammatory (carrageenan-induced
paw oedema test), analgesic (acetic acid-induced writhing test in mice), and antipyretic
(Brewer’s yeast-induced pyrexia test in mice) activities against control (normal saline) and relevant
reference standard drugs. Docking analyses were also performed to assess possible protein–ligand
interactions.
Results: The test compounds were non-toxic at doses of 50, 100 and 150 mg/kg body weight, ip.
Pharmacological evaluation revealed that the test compounds, TC-I through TC-IV, had significant anti-inflammatory
and peripheral analgesic activities (p < 0.001). An antipyretic test showed that TC-I, -II,
and -III showed highly significant antipyretic activities at all doses tested. TC-IV at 20 and 30 mg/kg
body weight exhibited significant antipyretic activities (p < 0.05), while at 50 mg/kg body weight, the
activity was highly significant (p < 0.001). Molecular modelling revealed strong inhibitory interactions
with docking scores of 116.2, 128.8, 144.2, and 136.0 kcal/mol, respectively, in comparison with the
reference ligand, flurbiprofen (94.9 kcal/mol).
Conclusion: The dimerised lead drug molecules showed significant anti-inflammatory, analgesic, and
antipyretic activities in animals and may further be explored as potential new drug candidates for
inflammatory conditions.
Keywords
Analgesic; Anti-inflammatory; Antipyretic; Arylpropionic acid; COX-2 inhibitors; Molecular docking
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