title: Evaluation of selected antitumor agents as subversive substrate and potential inhibitor of trypanothione reductase: an alternative approach for chemotherapy of Leishmaniasis.
abstract: Trypanothione reductase (TryR) is a validated drug target against Leishmaniasis. Using integrated computational and experimental approaches, the authors report doxorubicin and mitomycin C, known antitumor agents, as novel inhibitors of TryR of leishmania parasite. Interestingly, these compounds also act as subversive substrates and subvert the physiological function of enzyme by converting it from an anti-oxidant to a pro-oxidant. Possible mechanism of subversive substrate is discussed. Both doxorubicin and mitomycin C show significant effect on redox homeostasis of the parasite and high-leishmanicidal activity. The toxicity studies as well as available toxicity data in literature indicate these compounds to have acceptable toxicity in limited dose.
authors.affiliation: Department of Biotechnology, Indian Institute of Technology Guwahati, Assam, India.
authors.forename: Anil Kumar
authors.initials: AK
authors.lastname: Shukla
authors.forename: Sanjukta
authors.initials: S
authors.lastname: Patra
authors.forename: Vikash Kumar
authors.initials: VK
authors.lastname: Dubey
mesh_terms: D000981:Antiprotozoal Agents / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007896:Leishmaniasis / Q000188:drug therapy*; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D000981:Antiprotozoal Agents; D009247:NADH, NADPH Oxidoreductases; C049608:trypanothione reductase