New Insights into the Mechanism of Action of the Cyclopalladated Complex (CP2) in<i>Leishmania</i>: Calcium Dysregulation, Mitochondrial Dysfunction, and Cell Death
Ángela María Arenas Velásquez, Paula J. Bartlett, Irwin A.P. Linares, Thaís G. Passalacqua, Daphne D. L. Teodoro, Kely Braga Imamura, Stela Virgílio, Luíz Ricardo Orsini Tosi, Aline de Lima Leite, Marília Afonso Rabelo Buzalaf, Jecika Maciel Velasques, Adelino V.G. Netto, Andrew P. Thomas, Márcia A. S. Graminha
Abstract
mitochondrial membrane potential, and promotes apoptotic-like features in promastigotes, leading to necrosis, or directs programmed cell death (PCD)-committed cells toward necrotic-like destruction. Moreover, CP2 reduces the parasite load in both liver and spleen in Leishmania infantum-infected hamsters when treated for 15 days with 1.5 mg/kg body weight/day CP2, expanding its potential application in addition to the already known effectiveness on cutaneous leishmaniasis for the treatment of visceral leishmaniasis, showing the broad spectrum of action of this cyclopalladated complex. The data presented here bring new insights into the CP2 molecular mechanisms of action, assisting the promotion of its rational modification to improve both safety and efficacy.