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Antimicrobial Agents and Chemotherapy, December 2005, p. 5123-5126, Vol. 49, No. 12
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.12.5123-5126.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Antichagasic Activity of Komaroviquinone Is Due to Generation of Reactive Oxygen Species Catalyzed by Trypanosoma cruzi Old Yellow Enzyme

Nahoko Uchiyama,1,7 Zakayi Kabututu,2 Bruno K. Kubata,3 Fumiyuki Kiuchi,4 Michiho Ito,1 Junko Nakajima-Shimada,5 Takashi Aoki,5 Kei Ohkubo,6 Shunichi Fukuzumi,6 Samuel K. Martin,3 Gisho Honda,1 and Yoshihiro Urade2*

Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan,1 Department of Molecular Behavioral Biology, Osaka Bioscience Institute, Osaka 565-0874, Japan,2 United States Army Medical Research Unit-Kenya, Unit 64109, APO AE 09831-64109, Kenya,3 Tsukuba Medicinal Plant Research Station, National Institute of Health Sciences, Tsukuba 305-0843, Japan,4 Department of Molecular and Cellular Parasitology, Juntendo University School of Medicine, Tokyo 113-8421, Japan,5 Department of Material and Life Science, Graduate School of Engineering, Osaka University, SORST, JST, Osaka 565-0871, Japan,6 Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts, Kyoto 610-0395, Japan7

Received 14 June 2005/ Returned for modification 22 July 2005/ Accepted 20 September 2005

A novel potent trypanocidal diterpene, komaroviquinone, was reduced by Trypanosoma cruzi old yellow enzyme (TcOYE) to its semiquinone radical. The reductase activity in trypanosome lysates was completely immunoabsorbed by anti-TcOYE antibody. Since TcOYE is expressed throughout the T. cruzi life cycle, komaroviquinone is an interesting candidate for developing new antichagasic drugs.

* Corresponding author. Mailing address: Department of Molecular Behavioral Biology, Osaka Bioscience Institute, 6-2-4 Furuedai, Suita, Osaka 565-0874, Japan. Phone: (81)-6-6872-4851. Fax: (81)-6-6872-2841. E-mail: uradey{at}obi.or.jp.

Antimicrobial Agents and Chemotherapy, December 2005, p. 5123-5126, Vol. 49, No. 12
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.12.5123-5126.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.





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