Naphthoquinone derivatives exhibit apoptosis-like effect and anti-trypanosomal activity against Trypanosoma evansi

Trypanosoma evansi is an extracellular flagellate blood protozoan parasite and an etiological agent of animal trypanosomosis. Presently, only a few drugs are registered and have been used for the treatment of animal trypanosomosis, but they show severe toxic effects and also face the problem of drug resistance. Naphthoquinones (NTQ) are considered as fortunate structures in the field of medicinal chemistry as they have been reported for their antitrypanosomal potential against other trypanosomes-T. brucei and T. cruzi. In the present study, six naphthoquinones (NTQ1-NTQ6) derivatives were evaluated for anti-trypanosomal activity by demonstrating their growth inhibitory effect against T. evansi. All NTQs significantly (p < 0.001) exhibited activity against parasite growth and multiplication with IC50 values of 11.48 μM, 373.6 μM, 12.97 μM, 21.97 μM, 18.19 μM and 5.758 μM but NTQ1, NTQ3 and NTQ6 were selected based on their IC50 value for further studies. The dose-and time-dependent morphological effect on parasite was evaluated including the measurement of reactive oxygen species (ROS) by spectrofluorometery and measurement of apoptosis by flow cytometry. The selected NTQs exhibited a significant production of ROS and displayed a significant AV+ and PI+ labelled cells in the axenic culture of T. evansi than quinapyramine methyl sulphate (QPS), as reference control. NTQs also showed more cytotoxic effect on horse peripheral blood mononuclear cells as compare to QPS. Therefore, we confirmed the antitrypanosomal activity and apoptotic-like mechanism of NTQs in an axenic culture of T. evansi.