In-silico Analysis and Anti-inflammatory Evaluation of Synthesized Amide Derivatives of Long-chain Fatty Acids

In-silico Analysis and Anti-inflammatory Evaluation of Synthesized Amide Derivatives of Long-chain Fatty AcidsBackground: The search for more active and less toxic anti-inflammatory drugs is the desire of every medicinal chemist.Amide derivatives of fatty acids (FAs) have diverse biological functions. Objectives:The search for more active and less toxic anti-inflammatory drugs is the desire of every medicinal chemist.Amide derivatives of FAs have diverse biological functions. Methods:The current study conducted an in-silico molecular docking analysis using PDB ID: 6DII on synthesized amide derivatives of long-chain FAs (LCFAs) and evaluated and correlated their anti-inflammatory and anti-nociceptive biological mechanisms with those of acetylsalicylic acid as a standard.The synthesis was achieved using glycine, -alanine, -aminobutyric acid (GABA), and palmitoyl chloride.The raw paw edema model was used to assess the anti-inflammatory and analgesic properties. Results:The anti-inflammatory assessment revealed a dose-dependent bioactivity from 20 mg/kg to 50 mg/kg; further increments in the dose led to decreased activity.For the analgesic activity, at 100 mg/kg, N-palmitoyl glycine exhibited 83.2% inhibition of writhing compared to 74.3% inhibition of the standard drug, aspirin (100 mg/kg).The molecular docking studies showed that N-palmitoyl alanine had the highest protein binding affinity, followed by N-palmitoyl, GABA, and N-palmitoyl glycine, higher than acetylsalicylic acid.The compounds interacted with the protein via specific functional groups and protein amino acid residues. Conclusion:The ability of these amide derivatives of LCFAs to biologically inhibit the inflammatory and nociceptive pathways could be attributed to the presence of N-H, C=O, and OH groups, which bind to the GLY-255, THR-300, GLY-302, and ASP-207 residues.