Docking Studies and Anti-inflammatory Activity of β-Hydroxy-β-arylpropanoic Acids

Molecules

Sanda P. Dilber¹  Silva Lj. Dobric²  Zorica D. Juranic³  Bojan D. Markovic¹  Sote M. Vladimirov¹ 

[1] Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11000 Belgrade, Serbia;Institute for Scientific Information, Crnotravska 17, 11000 Belgrade, Serbia;Institute for Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade, Serbia

关键词: β-Hydroxy-β-arylalkanoic acids;    Reformatsky reaction;    anti-inflammatory activity;    molecular docking simulations;    COX-2 selective inhibitor;   

DOI  :  10.3390/molecules13030603

来源: mdpi

【 摘 要 】

The article describes a two-step synthesis of diastereomeric 3-hydroxy-2-methyl-3-(4-biphenylyl)butanoic acids. In the first step an intermediate α-bromo propanoic acid 1-ethoxyethyl ester was synthesized. The second step is a new modified Reformatsky reaction in presence of Zn in tetra­hydro­furan (THF) at –5 to 10 °C between the previously synthesized intermediate and 4-acetylbiphenyl. Synthesis of the other studied β-hydroxy-β-arylpropanoic acids has already been reported. These β-hydroxy-β-arylpropanoic acids belong to the arylpropanoic acid class of compounds, structurally similar to the NSAIDs such as ibuprofen. The anti-inflammatory activity and gastric tolerability of the synthesized compounds were evaluated. Molecular docking experiments were carried out to identify potential COX-2 inhibitors among the β-hydroxy-β-aryl-alkanoic acids class. The results indicate that all compounds possess significant anti-inflammatory activity after oral administration and that the compounds 2-(9-(9-hydroxy-fluorenyl))-2-methylpropanoic acid (5) and 3-hydroxy-3,3-diphenyl-propanoic acid (3) possess the strongest anti-inflammatory activity, comparable to that of ibuprofen, a standard NSAID, and that none of tested substances or ibuprofen produced any significant gastric lesions.

【 授权许可】

Unknown   
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