SYNTHESIS, CHARACTERIZATION, IN SILICO ,IN VITRO ,ANTIPLATELET AGGREGATION AND PHOSPHOLIPASE A2 STUDIES OF (E)-2(BENZYLIDENEAMINO)-4-METHYLPENTANOIC ACID, (E)-2-((1-PHENYLETHYLIDENE)AMINO)PROPANOIC ACID AND (E)-4-METHYL-2-((1-PHENYLETHYLIDENE)AMINO)PENTANOIC ACID.

Abstract

This research investigated the synthesis, characterization, in silico, in vitro antiplatelet aggregation and Phospholipase A₂(PLA₂) activities of Schiff base derivatives (E)-2-(benzylideneamino)-4-methylpentanoic acid, (E)-2-((1-phenylethylidene)amino) propanoic acid and (E)-4-methyl-2-((1-phenylethylidene)amino)pentanoic acid. The Schiff base derivatives were prepared from the condensation reaction between selected amino acids and aromatic aldehydes/ketones under controlled conditions. The FTIR, ¹HNMR and HRMS spectra were in agreement with the assigned structures, confirming the formation of imine functional group, which confirmed the successful formation of the target compounds. In silico molecular docking studies were carried out to confirm the binding interactions of the synthesized compounds with COX-2 and PLA₂ enzymes. The results revealed favorable binding affinities, with (E)-2-(benzylideneamino)-4-methylpentanoic acid exhibiting the strongest interaction for in silico antiplatelet study and (E)-2-((1-phenylethylidene)amino)propanoic acid exhibiting the strongest interaction for in silico phospholipase A₂ study. In vitro antiplatelet aggregation assays revealed that (E)-2-(benzylideneamino)-4-methylpentanoic acid showed the highest inhibitory activity achieving 70% inhibition at 8 mg/mL while aspirin achieved 80% inhibition at 8 mg/mL. Furthermore, the PLA₂ inhibitory assay revealed that (E)-2-((1-phenylethy lidene)amino)propanoic acid and (E)-4-methyl-2-((1-phenylethylidene)amino) pentanoic acid achieved a complete inhibition at 400 µg/mL, while (E)-2-(benzylidene amino)-4-methylpentanoic acid reached 100% inhibition at 800 µg/mL and this was tested in comparison to Prednisolone which maintained 100% inhibition across all concentrations tested.