Phyloactivity-based screening of coumarin-containing plants against Trypanosoma cruzi and target identification

Chagas disease is caused by the protozoan parasite, Trypanosoma cruzi. It is a neglected tropical disease prevalent in Latin America. Chemotherapy with benznidazole or nifurtimox is effective when administered in the acute stage but the efficacy is lower in the chronic phase of the disease and these drugs become toxic [1]. Among rural communities with no accessibility to conventional medicine, intervention with botanical drugs seems to be a possible alternative against parasitic diseases [2]. We performed a systematic analysis to challenge this hypothesis starting with an ethnobotanical/pharmacological fieldwork among indigenous groups in the Bolivian Chaco where Chagas disease is hyper endemic. From the antichagasic plant taxa and chemotaxonomic clusters, we identified several natural product scaffolds via bioactivity-guided isolation [3]. We are currently interested in the antichagasic coumarin-containing plants and aim to identify the potential targets of coumarins in T. cruzi. To this aim, a library of 23 coumarins-containing plant taxa were tested. To assess the anti-trypanosomal activity, we have established an in vitro parasite release assay to quantitate the trypomastigotes released from infected host cells by flow cytometry. We have synthesized clickable coumarin probes to identify the possible targets in T. cruzi trypomastigotes.

Publication History

Article published online:
13 December 2021

• References

• 1 Rassi Jr, Anis Rassi JAM-N, Lancet. Chagas disease. The Lancet. 2018
• 2 Salm A, Gertsch J. Cultural perception of triatomine bugs and Chagas disease in Bolivia: a cross-sectional field study. Parasit Vectors [Internet] 2019; 12 (01) 291 Available from https://www.ncbi.nlm.nih.gov/pubmed/31182163
• 3 Salm A, Krishnan SR, Collu M, Danton O, Hamburger M, Leonti M. et al. Phylobioactive hotspots in plant resources used to treat Chagas disease. iScience 2021; 24 (04) 102310