Docking Studies, Synthesis and Biological Evaluation of beta-aryl-beta-hydroxy Propanoic Acids for Anti-inflammatory Activity
| Autor: | Sote Vladimirov, Marina Milenković, Bojan Marković, Sanda Dilber, Jasmina Brborić, Jelena Kotur-Stevuljevic, Jelena Savić |
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| Rok vydání: | 2017 |
| Předmět: |
medicine.drug_class
Stereochemistry Protein Conformation Pharmacology 030226 pharmacology & pharmacy Anti-inflammatory 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine In vivo Drug Discovery medicine Animals Edema Cyclooxygenase Inhibitors Reformatsky reaction Aryl Anti-Inflammatory Agents Non-Steroidal Ibuprofen 3. Good health Rats Molecular Docking Simulation Tolerability chemistry Docking (molecular) Cyclooxygenase 2 030220 oncology & carcinogenesis Cyclooxygenase 1 Liver function Propionates medicine.drug |
| Zdroj: | Medicinal Chemistry |
| Popis: | Background: Nonsteriodal anti-inflammatory drugs (NSAIDs) are numerous and widely used for more than 60 years, but there is still a strong need for developing novel selective NSAIDs. The need is justified by the fact that nonselective NSAIDs can produce serious gastric side effects and that some of the selective NSAID are withdrawn due to their cardiotoxic side effects. Methods: Eight beta-hydroxy-beta-arylpropanoic acids, which belong to the arylpropanoic acid class of compounds, structurally similar to some nonsteroidal anti-inflammatory drugs (NSAIDs), were docked into 3D catalytic site of both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). Seven out of those eight acids were synthesized using already published modification of Reformatsky reaction additionally optimized by increasing temperature. Synthesized compounds were tested in vivo in order to elucidate anti-inflammatory activity, gastric tolerability and impact on liver function of rats. Results: Results of docking studies have indicated that all compounds have potential to selectively inhibit COX-2 isoform, but that the compounds containing polar substituents on phenyl ring are better inhibitors. Results of carrageenan-induced rat paw oedema test have shown that all compounds exhibit dose dependence and good gastric tolerability and none of the tested compounds have shown negative effect on liver function compared to ibuprofen. Conclusion: The compound containing polar nitro group in para position has shown the best docking results, anti-inflammatory activity, low hepatotoxicity and good gastric tolerability. |
| Databáze: | OpenAIRE |
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