Dicentrine, an Aporphine Alkaloid From Ocotea langsdorffii , Induces Mitochondrial Dysfunction and Oxidative Stress in Leishmania (L.) infantum
Camila S. de Freitas, Eduardo Oliveira S. da Silva, Daniela C. Tristão, Guilherme M. Antar, Daniela P. Lage, Dóris M. Abrão, Luciana M. Ribeiro Antinarelli, Elaine S. Coimbra, João Henrique G. Lago, Eduardo A. F. CoelhoABSTRACT
Dicentrine, an aporphine alkaloid isolated from Ocotea langsdorffii , was evaluated for its in vitro antileishmanial activity against Leishmania (L.) infantum , Leishmania (L.) amazonensis , and Leishmania (V.) braziliensis . Cytotoxicity was assessed in murine peritoneal macrophages, and the mechanism of action was investigated in L. (L.) infantum promastigotes by evaluating mitochondrial membrane potential (Δ Ψ m), reactive oxygen species (ROS) production, and plasma membrane integrity. Dicentrine exhibited potent activity against promastigote and intracellular amastigote forms, with EC 50 values ranging from 0.86 to 1.64 µg/mL. The compound showed low cytotoxicity toward macrophages (CC 50 = 162.5 µg/mL), resulting in high selectivity indices (up to 188.3). Mechanistic studies revealed significant disruption of Δ Ψ m and a dose‐dependent increase in ROS production, indicating mitochondrial dysfunction and oxidative stress as key events in parasite death. These findings highlight dicentrine as a promising lead for antileishmanial drug development.