Inhibition of Trypanosoma evansi Protein-Tyrosine Phosphatase by Myristic Acid Analogues Isolated from Khaya senegalensis and Tamarindus indica

• Published in: Journal of experimental pharmacology 2019-12, Vol.11, p.135-148
• Main Authors: Dingwoke, Emeka John, Adamude, Fatima Amin, Chukwuocha, Chimee Ethel, Ambi, Ahmed Adamu, Nwobodo, Nwobodo Ndubuisi, Sallau, Abdullahi Balarabe, Nzelibe, Humphrey Chukwuemeka
• Format: Article
• Language: English
• Subjects: Amino acids; Analysis; Animals; Bioassays; Cattle; Cell cycle; Cellular signal transduction; Chromatography; Disease transmission; Enzymes; Fatty acids; Fractionation; Gas chromatography; Glycoproteins; Health aspects; Immune system; Infection; Infections; inhibition; Insects; khaya senegalensis; Livestock; myristic acid analogues; non-competitive; Original Research; Parasites; Parasitic diseases; Phenols (Class of compounds); Phosphatase; Phosphatases; Phytochemicals; protein-tyrosine phosphatase; Proteins; Protozoa; regulation; Saturated fatty acids; signal transduction; Spectroscopy; tamarindus indica; trypanosoma evansi; Trypanosomiasis; Tyrosine
• ISSN: 1179-1454; 1179-1454
• DOI: 10.2147/JEP.S226632

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 and on the enzymatic activity of protein-tyrosine phosphatase. 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 and . 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 of 0.67 mg/mL for and 2.17 mg/mL for . The kinetic parameters for the cleavage of para-nitrophenylphosphate by the enzyme showed a K of 3.44 mM and V of 0.19 µmol/min. Sodium orthovanadate, the enzymes' specific inhibitor, inhibited the enzyme competitively with of 0.20 mg/mL. Gas chromatography-mass spectrometry analysis of the stem bark bioactive fractions of and revealed the presence of myristic acid analogues. 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.