Synthesis, Anti-inflammatory and Anti-nociceptive Evaluation of Palmitoyl Benzamides

Purpose: To synthesize and characterize palmitoyl amino benzamides, and to evaluate them for possible anti-inflammatory and anti-nociceptive activities.
Methods: Palmitoyl amino benzamides were synthesized by the opening of isatoic anhydride ring with respective amino acids (glycine, β-alanine and γ-aminobutyric acid) and the condensation of the product with palmitoyl chloride. The final products were purified on column chromatography, eluting with dichloromethane/ethyl acetate. All the compounds were unequivocally characterized using the combination of infra red (IR), 1H and 13C (nuclear magnetic resonance (NMR), mass spectrometry (MS) and elemental analysis. In vivo anti-inflammatory and anti-nociceptive activities of the synthesized compounds at 20, 50 and 100mg/kg doses were carried out using carrageenan-induced paw oedema in rat and acetic acid-induced writhing in mice, respectively. Aspirin was used at a dose of 100mg/kg as the reference drug.
Results: The compounds were obtained in high yield (70 – 90 %) and purity. The anti-inflammatory results showed a poor activity for the compounds except o-palmitoylamino N-carboxyethyl benzamide which produced significant inhibition (p < 0.05) at a dose of 50 mg/kg (43.8 % oedema inhibition) while the reference drug, aspirin, showed 51.3 % inhibition. The anti-nociceptive study, however, showed good inhibition (p < 0.05) of acetic acid-induced writhing, with o-palmitoylamino N- carboxymethylbenzamide producing 86.2 % inhibition at 100 mg/kg dose compared with the reference drug (aspirin) which gave 74.3 % inhibition at 100 mg/kg.
Conclusion: The findings of this study indicate that the synthesized compounds, though displaying poor anti-inflammatory activity, do possess promising anti-nociceptive activity.

Keywords
Anti-inflammatory; Analgesic; Benzamide; Palmitoyl; Glycine; β-Alanine; γ-Aminobutyric acid; Aspirin