trans-Chalcone modulates Leishmania amazonensis infection in vitro by Nrf2 overexpression affecting iron availability.

trans-Chalcone modulates Leishmania amazonensis infection in vitro by Nrf2 overexpression affecting iron availability. Eur J Pharmacol. 2019 Apr 06;: Authors: Miranda-Sapla MM, Tomiotto-Pellissier F, Assolini JP, Machado Carloto AC, Taciane da Silva Bortoleti B, Gonçalves MD, Tavares ER, Henrique da Silva Rodrigues J, Colado Simão AN, Yamauchi LM, Nakamura CV, Verri WA, Costa IN, Conchon-Costa I, Pavanelli WR Abstract Leishmania parasites infect macrophages causing a wide spectrum of human diseases encompassing from cutaneous to visceral forms. The drugs currently used in leishmaniasis treatment are highly toxic and associated with acquired resistance. Seeking novel therapeutic targets, we conducted a comprehensive in vitro study to investigate the action of trans-chalcone (TC) against Leishmania amazonensis promastigote and amastigote forms. TC is a common precursor of flavonoids, however, no extensive research has been developed regarding its pharmacological properties. In silico predictions showed good drug-likeness potential for TC with high oral bioavailability and intestinal absorption. The TC-treatment had a direct action on promastigote forms leading to death by late apoptosis-like process resulting from an increased production of reactive oxygen species (ROS), loss of mitochondrial integrity, phosphatidylserine exposure, and damage on the membrane. Similar results were found for L. amazonensis-axenic amastigotes. The TC-tr...
Source: European Journal of Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharmacol Source Type: research