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Current Therapeutics, Their Problems and Thiol Metabolism as Potential Drug Targets in Leishmaniasis

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Leishmaniasis is one of the six diseases regarded most neglected by World Health Organization which is predominant in developing countries. Clinically, among the different forms of leishmaniasis, visceral leishmaniasis is the most fatal, serious disease, in which several organs of the body such as liver and spleen are affected. A limited number of drugs against leishmaniasis are available for the treatment and also, no suitable vaccine is available for the control of leishmaniasis. However, the drugs currently used for the treatment of leishmaniasis have serious side effects as well as drug resistance issues. Therefore, search for alternative drugs to treat leishmaniasis is widely pursued; often targeting the metabolic pathways of Leishmania which are either absent or different from the mammalian host and involved in survival, pathogenesis and drug resistance of parasite. Herein, we review the aspects of chemotherapy of leishmaniasis by synthetic and natural drugs, their mechanism of action, pharmacokinetics and involvement in the development of drug resistance. Furthermore, regulatory role of trypanothione as key molecule for redox homeostasis via antioxidant enzymes and proteins like tryparedoxin, tryparedoxin peroxidase, superoxide dismutase, and ascorbate peroxidase are presented. We have comprehensively discussed thiol metabolism as drug target and its role in parasite survival.
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Keywords: Antimonials; Leishmania; amphotericin B; drug resistance; glutaredoxin; pharmacokinetics; thiol metabolism; trypanothione; tryparedoxin

Document Type: Research Article

Publication date: November 1, 2016

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  • Current Drug Metabolism aims to cover all the latest and outstanding developments in drug metabolism and disposition. The journal serves as an international forum for the publication of timely reviews in drug metabolism. Current Drug Metabolism is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the latest and most important developments. The journal covers the following areas:

    In vitro systems including CYP-450; enzyme induction and inhibition; drug-drug interactions and enzyme kinetics; pharmacokinetics, toxicokinetics, species scaling and extrapolations; P-glycoprotein and transport carriers; target organ toxicity and interindividual variability; drug metabolism and disposition studies; extrahepatic metabolism; phase I and phase II metabolism; recent developments for the identification of drug metabolites and adducts.
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