en داروسازی و طب سنتی Medicine and traditional medicine پژوهشي Original Research <strong>Background</strong>: 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.<br> 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.<br> <strong>Methods</strong>: 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, &beta;-alanine, &gamma;-aminobutyric acid (GABA), and palmitoyl chloride. The raw paw edema model was used to assess the anti-inflammatory and analgesic properties.&nbsp;<br> <strong>Results</strong>: 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.<br> <strong>Conclusion</strong>: 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. Nociception, Anti-inflammatory Agents, Nociceptive, Carrageenan-induced edema, Molecular mechanisms 105 114 http://pbr.mazums.ac.ir/browse.php?a_code=A-10-820-2&slc_lang=en&sid=1 Samuel J. Bunu amuelbunu2@gmail.com 100319475328460011344 100319475328460011344 Yes Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmacy, Niger Delta University, Wilberforce Island, Nigeria. Haruna Baba babharun1@gmail.com 100319475328460011345 100319475328460011345 No Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmacy, University of Calabar, University of Calabar, Nigeria. Deghinmotei Alfred-Ugbenbo audeghinmotei@gmail.com 100319475328460011346 100319475328460011346 No Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Bayelsa Medical University, Yenagoa, Nigeria.