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

Molecules 2008, 13, 603-615 molecules ISSN 1420-3049 ? 2008 by MDPI /molecules Full Paper Docking Studies and Anti-inflammatory Activity of β-Hydroxy-β-arylpropanoic Acids Sanda P. Dilber 1, Silva Lj. Dobric 2, Zorica D. Juranic 3, Bojan D. Markovic 1, Sote M. Vladimirov 1 and Ivan O. Juranic 4,* 1 Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11000 Belgrade, Serbia 2 Institute for Scientific Information, Crnotravska 17, 11000 Belgrade, Serbia 3 Institute for Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade, Serbia 4 Faculty of Chemistry, University of Belgrade, P.O. Box 158, 11001 Belgrade, Serbia * Author to whom the correspondence should be addressed; E-mail: ijuranic@chem.bg.ac.yu Received: 18 February 2008; in revised form: 8 March 2008/ Accepted: 10 March 2008 / Published: 18 March 2008 Abstract: 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-pro