Screening natural product extracts against kinetoplastid parasites

The kinetoplastids parasites are a group of flagellated protozoan parasites characterized by the subcellular structure, kinetoplast. Trypanosoma spp and Leishmania spp are the most notable kinetoplastids with major impact on human and animal health. Human African Trypanosomiasis (HAT) caused by Trypansoma brucei and visceral leishmaniasis caused by Leishmania donovani affect mostly neglected segments of the populations. The toxicity and resistance for currently available drugs and depleted drug discovery pipeline, necessitate discovery of new drugs. Natural products are vast source of diverse drug molecules with novel chemotypes. A 384 well plate screening paradigm has been developed that covers the screening of natural products extracts against L. donovani promastigotes, L. donovani axenic amastigote, differentiated THP1 (Human Acute Monocytic Leukemia) cells infected with L. donovani amastigotes and also cytotoxicity against uninfected THP1 cells. In the initial phase 176 plant extracts, prepared from the North American plants, have been screened. Lead extracts Cupressus lawsoniana, Acer pensylvanicum, Verbesina virginica, were identified as new antitrypanosomal leads with significant selectivity. Further follow up evaluation of lead extracts is likely to identify drug leads with novel chemotypes.

Fig. 1: A- T. brucei trypamastigotes; B- L. donovani promastigotes; (C) L. donovani axenic amastigotes; (D) Uninfected THP1 cell and (E) A THP1 cell infected with L. donovani amastigotes; mM-macrophage nucleus.