in-silico analysis and anti-inflammatory evaluation of synthesized amide derivatives of long-chain fatty acids

Background: 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, β-alanine, γ-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.