Docking studies and anti-inflammatory activity of beta-hydroxy-beta-arylpropanoic acids

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Pharmacology

Background:

• Arylpropanoic acids are a class of compounds structurally related to nonsteroidal anti-inflammatory drugs (NSAIDs).
• There is ongoing interest in developing new NSAIDs with improved efficacy and reduced gastrointestinal side effects.

Purpose of the Study:

• To synthesize novel diastereomeric 3-hydroxy-2-methyl-3-(4-biphenylyl)butanoic acids.
• To evaluate the anti-inflammatory activity and gastric tolerability of synthesized beta-hydroxy-beta-arylpropanoic acids.
• To identify potential COX-2 inhibitors within this chemical class using molecular docking.

Main Methods:

• A two-step synthesis involving an alpha-bromo propanoic acid intermediate and a modified Reformatsky reaction with 4-acetylbiphenyl.
• In vitro and in vivo evaluation of anti-inflammatory activity and gastric tolerability.
• Molecular docking studies to predict COX-2 inhibition.

Main Results:

• All synthesized compounds exhibited significant anti-inflammatory activity upon oral administration.
• Compounds 2-(9-(9-hydroxy-fluorenyl))-2-methylpropanoic acid (5) and 3-hydroxy-3,3-diphenyl-propanoic acid (3) showed anti-inflammatory activity comparable to ibuprofen.
• No significant gastric lesions were observed for the tested compounds or ibuprofen.

Conclusions:

• The synthesized beta-hydroxy-beta-arylpropanoic acids represent a promising class of compounds for anti-inflammatory drug development.
• The findings suggest these compounds may offer a favorable therapeutic window with reduced gastrointestinal risks compared to traditional NSAIDs.