Pharmaceutical Research

, 28:2758

Mitochondria and Trypanosomatids: Targets and Drugs

Expert Review

DOI: 10.1007/s11095-011-0586-3

Cite this article as:
Fidalgo, L.M. & Gille, L. Pharm Res (2011) 28: 2758. doi:10.1007/s11095-011-0586-3

ABSTRACT

The family Trypanosomatidae, flagellated parasitic protozoa, is responsible for important infectious diseases in humans: sleeping sickness, Chagas diseases and leishmaniasis. Currently, development of effective vaccines against these parasites remains an unrealized goal, and clinical management is based on chemotherapeutics. Cost, toxicity and resistance problems of conventional drugs result in an urgent need to identify and develop new therapeutic alternatives. The sound understanding of parasites, biology is key for identifying novel lead structures and new drug targets. This article reviews current knowledge about mitochondrial drug targets and existing drugs against Trypanosoma and Leishmania. In the past, several targets in trypanosomatid mitochondria (electron transport chain, kDNA and topoisomerases, tRNA import and fatty acid synthesis) have been identified. It has been suggested that inhibition of certain targets is involved in triggering apoptosis by impairment of mitochondrial membrane potential and/or production of reactive oxygen species. The inhibitory mechanism of approved drugs, such as pentamidine, nifurtimox, artemisinin and atovaquone, is described in parallel with others products from preclinical studies. In spite of the large amount of genetic information, the analysis of the phenotype of the trypanosomatid mitochondrion in different life stages will remain a useful tool to design new active compounds with selective toxicity against these parasites.

KEY WORDS

drugLeishmaniamitochondriatargetTrypanosoma

ABBREVIATIONS

DIM

3,3′diindolylmethane

ETC

electron transport chain

FAS

fatty acid synthesis

FRD

fumarate reductase

gRNAs

short transcripts RNA

HAT

Human African Trypanosomiasis

kDNA

kinetoplastid DNA

MMP

mitochondrial membrane potential

NADH

nicotinamide adenine dinucleotide

NTDs

neglected tropical diseases

PCD

programmed cell death

RIC

rNA import complex

ROS

reactive oxygen species

TAO

Trypanosoma alternative oxidase

tRNA

transcription DNA

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Departamento de ParasitologíaInstituto de Medicina Tropical “Pedro Kourí”Ciudad HabanaCuba
  2. 2.Institute of Pharmacology and Toxicology Department of Biomedical SciencesUniversity of Veterinary MedicineViennaAustria