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

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-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.

Docking simulations, synthesis, and anti-inflammatory activity evaluation of 2-(N-alkyl)amino-3-nitroimidazo[1,2-a]pyridines

“…For instance, a recent study focused on the interaction of enzyme cyclooxygenase active site with a series of b-hydroxy-b-arylpropionic acid, structurally related to some COX inhibitors such as a-(4-isobutylphenyl)propanoic acid (ibuprofen) showed small DG values. Nevertheless, two of those propionic acids derivatives showed higher anti-inflammatory activity than ibuprofen itself in the carrageenan-induced edema model (Dilber et al, 2008).…”

Analyzing the Interaction of Andrographolide and Neoandrographolide, Diterpenoid Compounds From Andrographis Paniculata (Burm.F) Nees, to Cyclooxygenase-2 Enzyme by Docking Simulation

“…COX-1, meanwhile, appeared to shoulder the responsibility for the production of physiologically relevant prostanoids such as those in the stomach and platelets [2,3,4]. In inflammatory processes COX-2 is overexpressed [5]. The two isoforms are 63% identical and 77% similar at amino acids level.…”

Novel Fused 1h- Imidazo[1,2-B] Pyrazole Analogues as Anti-Inflammatory and Analgesic Agents With Their Molecular Docking Studies Against Cox-1 and Cox-2

“…The docked ligand-target complexes were analyzed carefully to identify the interactions and binding affinities. The docking score was recorded and docking poses were saved for reference [32]. expressed in mean ± SEM (n=6) significance levels * P<0.05, ** P < 0.01 and *** P < 0.001 as compared with the respective control.…”

“…Lipinski΄s rule-of-5 was calculated for all the compounds [31]. The 3D crystal structure of the COX-2 enzyme [1CX2] and COX-1 enzyme [1EQG] was retrieved from PDB database [32]. The COX-2 and COX-1 structure was first relaxed by 20,000 steps of minimization and a standard relaxation procedure using restrained Molecular Dynamics [33].…”