Scientific area
3.3 Health sciences
Discipline(s)
Tropical medicine
Parasitology
Infectious diseases
Project title
THIOL METABOLISM IN LEISHMANIA AND ITS POTENTIAL USE FOR LEISHMANIASIS THERAPY
Scientific Coordinator's name:
Ana M. Tomás
Scientific Coordinator's e-mail:
atomas@ibmc.up.pt
Principal R&D Unit:
Molecular Parasitology
Other R&D Units involved in the project:
Other R&D units involved in the project
Project keyword(s)
Leishmania; Trypanosomatids; parasite; trypanothione; redox; drug development.
Short abstract and comments
Leishmaniasis is a major health and veterinary concern. There is no satisfactory vaccine or treatment for leishmaniasis as all anti-parasitic drugs available suffer from drawbacks, namely host toxicity, complicated regimen of administration, high costs and drug resistance. Redox metabolism is dependent on a conjugate of glutathione and spermidine known as trypanothione [T(SH)2], and not, as in the parasite’s hosts, on glutathione. T(SH)2 is the main thiol of trypanosomatids being fundamental for preservation of their intracellular redox homeostasis and, directly or indirectly, required for a number of essential processes, e.g. peroxide (ROOH, ONNO-) metabolism, nuclear and mitochondrial DNA replication and detoxification of oxoaldehydes. Impelled by the possibility that molecules interacting with this thiol might provide adequate drug targets, we are identifying and characterizing parasite proteins involved in T(SH)2-dependent processes. Trypanothione synthetase (responsible for T(SH)2 synthesis), tryparedoxin [a thioredoxin-like oxidoreductase that transfers reducing equivalents from T(SH)2 to other proteins] and 2-cysteine peroxiredoxins have all been shown essential to the parasite and to infection; some of these are also known to be druggable. The three proteins are, thus, valid drug targets which we are now interested in exploting. For this, we are seeking partners with expertise in areas of drug development against trypanosomatids. Additional Leishmania potential targets, also redox proteins, are currently being studied.
Potential uses/indications
Development of anti-trypanosomatid drugs
Status
Ongoing
Partner Status: Seeking Partners?
Yes
Grant number (QREN, FP7, Eureka, etc)
Grant number (QREN, FP7, Eureka, etc)
Last edited on
2012-12-27 18:17:04