Development, characterization and pharmacological evaluation of amino acid prodrugs of (+)-Ibuprofen

Abstract

The current research work investigate the neuronal pathway associated with NSAIDs that lead to the reduction in the initiation and progression of neurodegenerative diseases such as Alzheimer’s disease, Parkinsonism etc. This research was developed amino acid prodrugs of the active enantiomer of ibuprofen, (+)-IBN and checks the pharmacological effects, neuroprotective effect, anti inflammatory effect and anti-ulcerogenic effect. The treatment using (+)-IBN reduced the action of micoglia and the release of cytokine especially TNFα that are mainly involved in the neurodegenerative process. (+)- IBN reduced the deposition of soluble beta amyloid plaque by inhibiting the amyloid precursor protein, beta-secretase 1 and also enhancing the degradation process of beta amyloid via induction of insulin degrading enzyme. (+)-IBN also showed the property that the reduction in the TAU misfolding process. Therefore, the synthesized (+)-IBN amino acid prodrugs treatment effectively produce neuroprotective action, both restoring memory realed risk factors and reversing multiple brain neuropathological hallmarks. The current research study developed the three amino acid prodrugs of (+)-ibuprofen by conjugating with L-phenyl alanine, L-tryptophan and L-tyrosine also the physico-chemical characterization and spectral characterization was done. This study modify the carboxylic acid functional group present in the NSAIDs that lead to the formation of prodrugs with enhanced anti-inflammatory activity, reduced side effects and protective effect against neurodegenerative processes.