ABSTRACT
BACKGROUND: Trypanosome infections still pose severe health and economic consequences, especially in the endemic regions of Sub-Saharan Africa. Trypanosome differentiation to the procyclic forms which lack the immune evasion mechanisms for survival in the bloodstream is prevented by tyrosine dephosphorylation which is catalyzed by protein-tyrosine phosphatase; thereby promoting survival of the parasites in the host. Inhibition of Protein-tyrosine phosphatase is a strategic therapeutic target that could attenuate trypanosomiasis. This study investigated the in vitro inhibitory effect of stem bark extracts of Khaya senegalensis and Tamarindus indica on the enzymatic activity of protein-tyrosine phosphatase. METHODS: All determinations were carried out following standard procedures for analytical experiments. The analogues of myristic acid that inhibited the enzymatic activity of protein-tyrosine phosphatase were isolated by bioassay-guided fractionation of stem bark extracts of Khaya senegalensis and Tamarindus indica. RESULTS: Analogues of myristic acid proved to be potent inhibitors of protein-tyrosine phosphatase. Double reciprocal (Lineweaver-Burk) plots of the initial velocity data indicated non-competitive inhibition with Ki of 0.67 mg/mL for Khaya senegalensis and 2.17 mg/mL for Tamarindus indica. The kinetic parameters for the cleavage of para-nitrophenylphosphate by the enzyme showed a KM of 3.44 mM and Vmax of 0.19 µmol/min. Sodium orthovanadate, the enzymes' specific inhibitor, inhibited the enzyme competitively with Ki of 0.20 mg/mL. Gas chromatography-mass spectrometry analysis of the stem bark bioactive fractions of Khaya senegalensis and Tamarindus indica revealed the presence of myristic acid analogues. CONCLUSION: Analogues of myristic acid are potent inhibitors of protein-tyrosine phosphatase that could be developed as trypanocide to inhibit the enzymatic activity of protein-tyrosine phosphatase in order to prevent transmission of trypanosomes.
