Title:Current Therapeutics, Their Problems and Thiol Metabolism as Potential Drug Targets in Leishmaniasis
Volume: 17
Issue: 9
Author(s): Kuljit Singh, Gaurav Garg and Vahab Ali
Affiliation:
Keywords:
Antimonials, amphotericin B, drug resistance, glutaredoxin, pharmacokinetics, Leishmania, trypanothione, thiol metabolism,
tryparedoxin.
Abstract: 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.
