Christophe Tratrat1, Michelyne Haroun1, Aliki Paparisva2, Charalmpos Kamoutsis3, Anthi Petrou2, Antonis Gavalas2, Phaedra Eleftheriou4, Athina Geronikaki2, Katharigatta N Venugopala1,5, Hafedh Kochkar6,7, Anroop B Nair1. 1. Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia. 2. School of Pharmacy, University of Thessaloniki, 54124 Thessaloniki, Greece. 3. School of Pharmacy, University of Patras, 26504 Patra, Greece. 4. Department of Biomedical Sciences, School of Health Sciences, International Hellenic University, 57400 Thessaloniki, Greece. 5. Department of Biotechnology and Food Technology, Durban University of Technology, Durban 4001, South Africa. 6. Department of Chemistry, College of Science, Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia. 7. Basic & Applied Scientific Research Center, Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia.
Abstract
BACKGROUND: Inflammation is a complex response to noxious stimuli promoted by the release of chemical mediators from the damaged cells. Metabolic products of arachidonic acid, produced by the action of cyclooxygenase and lipoxygenase, play important roles in this process. Several non-steroidal anti-inflammatory drugs act as cyclooxygenase inhibitors. However, almost all of them have undesired side effects. METHODS: Prediction of the anti-inflammatory action of the compounds was performed using PASS Program. The anti-inflammatory activity was evaluated by the carrageenan paw edema test. COX and LOX inhibitory actions were tested using ovine COX-1, human recombinant COX-2 and soybean LOX-1, respectively. Docking analysis was performed using Autodock. RESULTS: All designed derivatives had good prediction results according to PASS and were synthesized and experimentally evaluated. The compounds exhibited in vivo anti-inflammatory action with eleven being equal or better than indomethacin. Although, some of them had no or low inhibitory effect on COX-1/2 or LOX, certain compounds exhibited COX-1 inhibition much higher than naproxen and COX-2 inhibition, well explained by Docking analysis. CONCLUSIONS: A number of compounds with good anti-inflammatory action were obtained. Although, some exhibited remarkable COX inhibitory action this activity did not follow the anti-inflammatory results, indicating the implication of other mechanisms.
BACKGROUND:Inflammation is a complex response to noxious stimuli promoted by the release of chemical mediators from the damaged cells. Metabolic products of arachidonic acid, produced by the action of cyclooxygenase and lipoxygenase, play important roles in this process. Several non-steroidal anti-inflammatory drugs act as cyclooxygenase inhibitors. However, almost all of them have undesired side effects. METHODS: Prediction of the anti-inflammatory action of the compounds was performed using PASS Program. The anti-inflammatory activity was evaluated by the carrageenanpaw edema test. COX and LOX inhibitory actions were tested using ovine COX-1,human recombinant COX-2 and soybeanLOX-1, respectively. Docking analysis was performed using Autodock. RESULTS: All designed derivatives had good prediction results according to PASS and were synthesized and experimentally evaluated. The compounds exhibited in vivo anti-inflammatory action with eleven being equal or better than indomethacin. Although, some of them had no or low inhibitory effect on COX-1/2 or LOX, certain compounds exhibited COX-1 inhibition much higher than naproxen and COX-2 inhibition, well explained by Docking analysis. CONCLUSIONS: A number of compounds with good anti-inflammatory action were obtained. Although, some exhibited remarkable COX inhibitory action this activity did not follow the anti-inflammatory results, indicating the implication of other mechanisms.
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