ArticleAntimicrobial agents and chemotherapy2012
Induction of oxidative stress in Trypanosoma brucei by the antitrypanosomal dihydroquinoline OSU-40.
Article in Antimicrobial agents and chemotherapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Reproductive Impacts of African Animal Trypanosomiasis in West African Dwarf Goats-Mechanistic Insights into Trypanotolerance Survival-Fertility Trade-Off: A Systematic Review.Veterinary sciences · 2026Review
- Article
- Enolase Inhibitors as Early Lead Therapeutics againstPathogens (Basel, Switzerland) · 2023Article
- Kinetic Resolution of 2-Aryldihydroquinolines Using Lithiation - Synthesis of Chiral 1,2- and 1,4-Dihydroquinolines.Chemistry (Weinheim an der Bergstrasse, Germany) · 2023Article
- Association of Oxidative Stress with Neurological Disorders.Current neuropharmacology · 2022Article
- Isolation and Antitrypanosomal Characterization of Furoquinoline and Oxylipin fromBiomolecules · 2020Article
- Evaluation of Antitrypanosomal Dihydroquinolines for Hepatotoxicity, Mutagenicity, and Methemoglobin Formation In Vitro.International journal of toxicology · 2014Article
- DNA repair pathways in trypanosomatids: from DNA repair to drug resistance.Microbiology and molecular biology reviews : MMBR · 2014Review
- Cytosolic NADPH homeostasis in glucose-starved procyclic Trypanosoma brucei relies on malic enzyme and the pentose phosphate pathway fed by gluconeogenic flux.The Journal of biological chemistry · 2013Article
Corrections and comments
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Authors and funding
5 authors.
Funding
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Abstract
Dihydroquinoline derivative OSU-40 (1-benzyl-1,2-dihydro-2,2,4-trimethylquinolin-6-yl acetate) is selectively potent against Trypanosma brucei rhodesiense in vitro (50% inhibitory concentration [IC(50)], 14 nM; selectivity index, 1,700) and has been proposed to cause the formation of reactive oxygen species (ROS) in African trypanosomes (J. Fotie et al., J. Med. Chem. 53:966-982, 2010). In the present study, we sought to provide further support for the hypothesis that OSU-40 kills trypanosomes through oxidative stress. Inducible RNA interference (RNAi) was applied to downregulate key enzymes in parasite antioxidant defense, including T. brucei trypanothione synthetase (TbTryS) and superoxide dismutase B (TbSODB). Both TbTryS RNAi-induced and TbSODB RNAi-induced cells showed impaired growth and increased sensitivity toward OSU-40 by 2.4-fold and 3.4-fold, respectively. Decreased expression of key parasite antioxidant enzymes was thus associated with increased sensitivity to OSU-40, consistent with the hypothesis that OSU-40 acts through oxidative stress. Finally, the dose-dependent formation of free radicals was observed after incubation of T. brucei with OSU-40 utilizing electron spin resonance (ESR) spectroscopy. These data support the notion that the mode of antitrypanosomal action for this class of compounds is to induce oxidative stress.
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