title: Evaluation of plumbagin and its derivative as potential modulators of redox thiol metabolism of Leishmania parasite.
abstract: Trypanothione and trypanothione reductase (TryR)-based redox metabolism found in Leishmania and other trypanosomatids exemplify the unique features of this group of organisms. Its absence in mammalian hosts, together with the sensitivity of trypanosomes against oxidative stress, makes this enzyme a unique target for exploitation for potential antileishmanial chemotherapeutics. Plumbagin, a plant-derived naphthoquinone, is reported to possess antileishmanial properties by inhibiting TryR. We here report the kinetics of the inhibitory mechanism of plumbagin and its derivative, 2-methoxy 1, 4-naphthoquinone. Interestingly, apart from acting as inhibitor, these compounds also act as subversive substrates and subvert the physiological function of enzyme by converting it from an antioxidant to a prooxidant. Both naphthoquinones show a significant effect on redox homeostasis and results in increased reactive oxygen species, resulting in morphological changes and parasite death.
authors: Department of Biotechnology, Indian Institute of Technology Guwahati, Guwahati, Assam, 781039, India.
authors: Neha
authors: N
authors: Sharma
authors: Anil Kumar
authors: AK
authors: Shukla
authors: Mousumi
authors: M
authors: Das
authors: Vikash Kumar
authors: VK
authors: Dubey
mesh_terms: D000981:Antiprotozoal Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007891:Leishmania / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors; D009285:Naphthoquinones / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects; D013438:Sulfhydryl Compounds / Q000378:metabolism
chemical_list: D000981:Antiprotozoal Agents; D004791:Enzyme Inhibitors; D009285:Naphthoquinones; D013438:Sulfhydryl Compounds; C088404:2-methoxymethyl-1,4-naphthoquinone; D009247:NADH, NADPH Oxidoreductases; C049608:trypanothione reductase; C014758:plumbagin