title: Current Therapeutics, Their Problems and Thiol Metabolism as Potential Drug Targets in Leishmaniasis.
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.
authors.forename: Kuljit
authors.initials: K
authors.lastname: Singh
authors.forename: Gaurav
authors.initials: G
authors.lastname: Garg
authors.affiliation: Department of Biochemistry, Rajendra Memorial Research Institute of Medical Sciences, Agamkuan, Patna, 800007, India.
authors.forename: Vahab
authors.initials: V
authors.lastname: Ali
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D007891:Leishmania / Q000378:metabolism; D007896:Leishmaniasis / Q000188:drug therapy* / Q000378:metabolism; D013095:Spermidine / Q000031:analogs & derivatives / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism
chemical_list: D000981:Antiprotozoal Agents; D013438:Sulfhydryl Compounds; C044809:trypanothione; D005978:Glutathione; D013095:Spermidine