Mechanistic, in-silico and in vitro studies with nitrofurans reveal potent leishmanicidal activity and inhibition of trypanothione reductase

• Published in: International journal for parasitology -- drugs and drug resistance Vol. 28; p. 100605
• Main Authors: Andrés-Rodríguez, Julia, González-Montero, María-Cristina, García-Fernández, Nerea, Galano-Frutos, Juan-José, Rosa, Maria-Cristina de, Ferreira, Patricia, Pérez-Pertejo, María-Yolanda, Reguera, Rosa M., Balaña-Fouce, Rafael, García-Estrada, Carlos
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.08.2025; Elsevier
• Subjects: Animals; Antiprotozoal Agents - chemistry; Antiprotozoal Agents - pharmacology; Cell Line; Computer Simulation; Cyclic nitrofurans; Humans; Leishmania donovani; Leishmania donovani - drug effects; Leishmania donovani - enzymology; Leishmania infantum - drug effects; Leishmania infantum - enzymology; Leishmaniasis, Visceral - drug therapy; Leishmaniasis, Visceral - parasitology; Macrophages - drug effects; Macrophages - parasitology; Mice; Molecular docking; Molecular Docking Simulation; NADH, NADPH Oxidoreductases - antagonists & inhibitors; Nitrofurans - chemistry; Nitrofurans - pharmacology; Reactive Oxygen Species - metabolism; Trypanothione; Trypanothione reductase; Visceral leishmaniasis; CC50; AF; Leishmania donovani; BMDM; T[S]2; Cyclic nitrofurans; RMDS; Trypanothione; NTR; Molecular docking; DNDi; TryR; DCFH-DA; NTDs; Visceral leishmaniasis; GM-CSF; SI; VL; ROS; EC50; Trypanothione reductase

Visceral leishmaniasis caused by Leishmania infantum and Leishmania donovani is one of the neglected tropical diseases (NTDs) caused by trypanosomatids with treatment options limited to outdated drugs often causing adverse effects and promoting drug resistance. Previous antileishmanial drug discover...