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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.
AuthorsAnil Kumar Shukla, Sanjukta Patra, Vikash Kumar Dubey
JournalMolecular and cellular biochemistry (Mol Cell Biochem) Vol. 352 Issue 1-2 Pg. 261-70 (Jun 2011) ISSN: 1573-4919 [Electronic] Netherlands
PMID21359528 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antiprotozoal Agents
  • NADH, NADPH Oxidoreductases
  • trypanothione reductase
Topics
  • Antiprotozoal Agents (pharmacology)
  • Drug Evaluation, Preclinical
  • Humans
  • Leishmaniasis (drug therapy)
  • NADH, NADPH Oxidoreductases (antagonists & inhibitors, metabolism)
  • Substrate Specificity

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