Bioenergetics impairment of Trypanosoma cruzi by the antihypertensive manidipine: A drug repurposing strategy

Author(s)

Correa, Isabela Teresa Santos ^[1] ; da Costa-Silva, Thais Alves ^[2] ; Tempone, Andre Gustavo ^[1]

Affiliation

^[1] Adolfo Lutz Inst, Ctr Parasitol & Mycol, BR-01246000 Sao Paulo, SP - Brazil

^[2] Fed Univ ABC, Ctr Nat Sci & Humanities, BR-09210180 Santo Andre, SP - Brazil

• Document type: Journal article
• Source: Acta Tropica; v. 214, FEB 2021.
• Web of Science Citations: 0

Abstract

Considering the lack of effective and safe therapy for the treatment of Chagas disease, the antihypertensive drug manidipine (MDP) was in vitro evaluated against Trypanosoma cruzi. The bioenergetics of trypomastigotes was studied in the presence of the drug using fluorimetric and luminescent assays. Manidipine showed a potent antiparasitic activity, with IC50 values of 0.1 mu M (intracellular amastigotes) and 3 mu M (trypomastigotes), resulting in a promising selectivity index against the amastigotes (>1459). Using fluorimetric analysis, the drug showed depolarisation of the electric potential of the plasma membrane with no alteration of the permeability. A decrease in ATP levels suggested a bioenergetic alteration of the mitochondria, which was confirmed by the depolarisation of the mitochondrial membrane potential and a slight increase of the ROS levels. This is the first study to show the promising in vitro effectiveness of the antihypertensive MDP against T. cruzi, which may represent a candidate for future investigations in animal models. (AU)

• FAPESP's process: 18/10279-6 - Selection and Optimization of New Drug Candidates for Leishmaniasis and Chagas Disease
• Grantee: André Gustavo Tempone Cardoso
• Support Opportunities: Regular Research Grants