Our research focuses on the therapeutic potential of reactive oxygen species (ROS), with particular emphasis on their application in antiparasitic strategies. A central objective of our current work is the identification and mechanistic characterization of novel antileishmanial compounds. Leishmaniasis is a major global health concern, predominantly affecting populations in tropical and subtropical regions. However, its geographic distribution is expanding, partly due to climate change.
The disease is caused by protozoan parasites of the genus Leishmania and is transmitted to humans and other mammals, including dogs, through sandfly vectors. Consequently, leishmaniasis is of significant relevance to both human and veterinary medicine.
Our research explores the antileishmanial potential of organic endoperoxides, inspired by the established use of artemisinin-based compounds in malaria therapy. We investigate both synthetic and naturally occurring endoperoxides. Studied synthetic compounds include anthracene endoperoxides and 7-dehydrocholesterol endoperoxide, while natural representatives encompass artemisinin, ascaridole, and ergosterol endoperoxide.
To elucidate the mechanisms of action of these compounds, we employ a comprehensive set of biochemical and biophysical analyses. These include assessments of parasite viability, mitochondrial function, and cellular redox status, as well as studies on the modulation of activity by antioxidants and iron chelators.
Additional analyses involve sterol profiling and other metabolic parameters. Methodologically, our work integrates advanced techniques such as cellular oximetry, chromatographic methods, and electron spin resonance (ESR) spectroscopy, including spin trapping and spin labeling approaches. This research is conducted in close collaboration with our partners at the Institute of Tropical Medicine in Havana (Cuba) and Department of Pharmacology, Institute of Postgraduate Medical Education and Research in Kolkata (India), facilitating a strong translational and interdisciplinary framework.