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.
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Authors | Anil Kumar Shukla, Sanjukta Patra, Vikash Kumar Dubey |
Journal | Molecular and cellular biochemistry
(Mol Cell Biochem)
Vol. 352
Issue 1-2
Pg. 261-70
(Jun 2011)
ISSN: 1573-4919 [Electronic] Netherlands |
PMID | 21359528
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antiprotozoal Agents
- NADH, NADPH Oxidoreductases
- trypanothione reductase
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Topics |
- Antiprotozoal Agents
(pharmacology)
- Drug Evaluation, Preclinical
- Humans
- Leishmaniasis
(drug therapy)
- NADH, NADPH Oxidoreductases
(antagonists & inhibitors, metabolism)
- Substrate Specificity
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