Journal
VETERINARY PARASITOLOGY
Volume 290, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.vetpar.2021.109367
Keywords
Trypanosoma evansi; Surra; Naphthoquinones (NTQ); Growth inhibition assay; Apoptosis analysis; Reactive oxygen species; Cytotoxicity assay
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Funding
- Council of Scientific & Industrial Research (CSIR), New Delhi, Govt. of India [09/1258 (0001)/2019-EMR-1]
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Six naphthoquinone derivatives were evaluated for their anti-trypanosomal activity against T. evansi, with NTQ1, NTQ3, and NTQ6 showing the most potential. These NTQs exhibited significant production of ROS and characteristics of apoptosis in an axenic culture of T. 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. Naph-thoquinones (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 mu M, 373.6 mu M, 12.97 mu M, 21.97 mu M, 18.19 mu M and 5.758 mu M 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 spectrofluommetery 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.
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