Docking Studies, Synthesis and Biological Evaluation of β-aryl-β-hydroxy Propanoic Acids for Anti-inflammatory Activity

Title:Docking Studies, Synthesis and Biological Evaluation of β-aryl-β-hydroxy Propanoic Acids for Anti-inflammatory Activity

Volume: 13 Issue: 2

Author(s): Jelena Savic, Sanda Dilber, Marina Milenkovic, Jelena Kotur-Stevuljevic, Bojan Markovic, Sote Vladimirov and Jasmina Brboric

Affiliation:

Keywords: Molecular docking studies, reformatsky reaction, β-hydroxy-β-arylpropanoic acids, COX-2 selective inhibitor, antiinflammatory activity, rat paw oedema, liver enzymes, malonyldialdehyde.

Abstract: 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by the fact that nonselective NSAIDs can produce serious gastric side effects and that some of the selective NSAID are withdrawn due to their cardiotoxic side effects.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 β-hydroxy-β-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.

Cite this article as:

Savic Jelena, Dilber Sanda, Milenkovic Marina, Kotur-Stevuljevic Jelena, Markovic Bojan, Vladimirov Sote and Brboric Jasmina, Docking Studies, Synthesis and Biological Evaluation of β-aryl-β-hydroxy Propanoic Acids for Anti-inflammatory Activity, Medicinal Chemistry 2017; 13 (2) . https://dx.doi.org/10.2174/1573406412666160907150247

DOI https://dx.doi.org/10.2174/1573406412666160907150247	Print ISSN 1573-4064
Publisher Name Bentham Science Publisher	Online ISSN 1875-6638