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Tropical Disease Center

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Research Synopsis

     The Tropical Disease Research Center is evaluating the in vitro and in vivo anti-malarial and anti-trypanosomal activities of natural materials provided by our institute to develop promising treatments for protozoal diseases including malaria and African trypanosomiasis. We also search for the inhibitors of targetable protozoa-specific enzymes and investigate the modes of action of the anti-protozoal compounds we have found.

1. Search for anti-malarial drugs (post-WHO project)

2. Search for anti-trypanosomal drugs (post-DNDi project)

3. Search for the inhibitors of protozoa-specific enzymes

4. Analysis of the modes of action of discovered anti-protozoal compounds

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Staff

Name position
Iwatuki Masato  Lecturer iAssistant Chief of Centerj
Ishiyama Aki  Researcher
Otoguro Kazuhiko  Researcher

Research Results

  1. K. Otogutro, A. Ishiyama, M. Iwatsuki, M. Namatame, A. Nishihara-Tsukashima, H. Kiyohara, T. Hashimoto, Y. Asakawa, S. Omura, H. Yamada. : In vitro antitrypanosomal activity of bis(bibenzyl)s and bibenzyls from liveworts against Trypanosoma brucei., J. Nat. Med., 66, 377-382 (2012)
  2. K. Otoguro, M. Iwatsuki, A. Ishiyama, M. Namatame, A. Nishihara-Tsukashima, H. Kiyohara, T. Hashimoto, Y. Asakawa, S. Omura, H. Yamada. : In vitro antitrypanosomal activity of some phenolic compounds from propolis and lactones from Fijian Kawa (Piper methysticum)., J. Nat. Med., 16, 558-561 (2012)
  3. J. Hashida, M. Niitsuma, M. Iwatsuki, M. Mori, A. Ishiyama, M. Namatame, A. Nishihara-Tsukashima, A. Matsumoto, A. Ismet, Y. Takahashi, H. Yamada, K. Otoguro, K. Shiomi, S. Omura. : Panowamycins A and B, new antitrypanosomal isochromans produced by Streptomyces sp. K07-0010., J. Antibiot., 65, 197-202 (2012)
  4. H. Oguri, H. Mizoguchi, H. Oikawa, A. Ishiyama, M. Iwatsuki, K. Otoguro, S. Omura. : Parallel and four-step synthesis of natural-product-inspired scaffolds through modular assembly and divergent cyclization., Bellstein J. Org. Chem., 8, 930-340 (2012)
  5. A. Tsutsui, T. Hirose, A. Ishiyama, M. Iwatsuki, A. Yokota, H. Maruyama, H. Matsui, K. Otoguro, H. Hanaki, S. Omura, T. Sunazuka. : Antimalarial C-9 oxime derivatives from desmycosin, produced by click chemistry., J. Antibiot. (2012) doi: 10.1038/ja.2012.113

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  1. M. Iwatsuki, A. Nishihara-Tsukashima, A. Ishiyama, M. Namatame, Y. Watanabe, S. Handasah, H. Pranamuda, B. Marwoto, A. Matsumoto, Y. Takahashi, K. Otoguro, S. Omura, : Jogyamycin, a new antiprotozoal aminocyclopentitol antibiotic, produced by Streptomyces sp. a-WM-JG-16.2,J. Antibiot.,65,169-171(2012)
  2. A. Ishiyama, K. Otoguro, M. Iwatsuki, M. Namatame, A. Nishihara-Tsukashima, Y. Takahashi, H. Onodera, H. Yamada, S. Omura, : In vitro antitrypanosomal activity of five low-MW antibiotics,J. Antibiot.,65,113-114(2012)
  3. K. Otoguro, M. Iwatsuki, A. Ishiyama, M. Namatame, A. Nishihara-Tukashima, H. Kiyohara, T. Hashimoto, Y. Asakawa, S. Omura, H. Yamada, : In vitro antitrypanosomal activity of plant terpenes against Trypanosoma brucei, Phytochemistry,72,2024-2030(2011)
  4. Y. Inahashi, M. Iwatsuki, A. Ishiyama, M. Namatame, A. Nishihara-Tsukashima, A. Matsumoto, T. Hirose, T. Sunazuka, H. Yamada, K. Otoguro, Y. Takahashi, S. Omura, K. Shiomi, : Spoxazomicins A-C, novel antitrypanosomal alkaloids produced by an endophytic actinomycete, Streptosporangium oxazolinicum K07-0460T, J. Antibiot.,64,303-307(2011)
  5. T. Ishii, K. Nonaka, M. Iwatsuki, R. Masuma, S. Omura, K. Shiomi,Virgaricin produced by Virgaria sp. FKI-4860,J . Antibiot.,65,139-141(2012)
  6. K. Nonaka, T. Abe, M. Iwatsuki, M. Mori, T. Yamamoto, K. Shiomi, S. Omura, R. Masuma, : Enhancement of metabolites productivity of Penicillium pinophilum FKI-5653, by co-culture with Trichoderma harzianum FKI-5655,J. Antibiot.,64,769-774(2011)
  7. M. Iwatsuki, T. Ishimori, T. Yamamoto, K. Takata, M. Mori, K. Nonaka, R. Masuma, Y. Hayakawa, H. Hanaki, K. Shiomi, S. Omura, : Biverlactones A-D, new circumventors of arbekacin resistance in MRSA, produced by Penicillium sp. FKI-4429,Tetraheadron,67,6644-6648(2011)
  8. T. Hirose, M. Iwatsuki, S. Omura, T. Sunazuka, : Isolation, total synthesis and determination of the absolute configuration of guadinomines, potent inhibitors of a bacterial Type III secretion system,—L‹@‡¬‹¦‰οŽ,69,775-788(2011)
  9. K. Nonaka, R. Masuma, M. Iwatsuki, K. Shiomi, K. Otoguro and S. Omura, : Penicillium viticola, a new species isolated from a grape in Japan, Mycoscience,52,338-343(2011)
  10. Nonaka, K: Masuma, R. Iwatsuki, M. Shiomi, K. Otoguro, K. & S. Omura, : Penicillium viticola, a new species isolated from a grape in Japan.,Mycoscience,52,338-343(2011)
  11. H. Oguri, T. Hiruma, Y. Yamagishi, H. Oikawa, A. Ishiyama, K. Otoguro, H. Yamada, S. Omura, : Generation of anti-trypanosomal agents through concise synthesis and structural diversification of sesquiterpene analogues,J. Am. Chem .Soc.,133,7096-7105(2011)

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  1. A. Ishiyama, M. Iwatsuki, M. Namatame, A. Nishihara-Tsukashima, T. Sunazuka, Y. Takahashi, S. Omura, K. Otoguro, : Borrelidin, a potent antimalarial: stage-specific inhibition profile of synchronized cultures of Plasmodium falciparum, J. Antibiot.,64,381-384(2011)
  2. M. Iwatsuki, S. Takada, M. Mori, A. Ishiyama, M. Namatame, A. Nishihara-Tsukashima, K. Nonaka, R. Masuma, K. Otoguro, K. Shiomi, S. Omura, : In vitro and in vivo antimalarial activity of puberulic acid and its new analogs, viticolins A-C, produced by Penicillium sp. FKI-4410,J. Antibiot.,64,183-188(2011)
  3. M. Niitsuma, J. Hashida, M. Iwatsuki, M. Mori, A. Ishiyama, M. Namatame, A. Nishihara-Tsukashima, A. Matsumoto, Y. Takahashi, H. Yamada, K. Otoguro, K. Shiomi, S. Omura, : Sinefungin VA and dehydrosinefungin V, new antitrypanosomal antibiotics produced by Streptomyces sp. K05-0178,J. Antibiot.,63,673-679(2010)
  4. M. Iwatsuki, K. Otoguro, A. Ishiyama, M. Namatame, A. Nishihara-Tukashima, J. Hashida, T. Nakashima, R. Masuma, Y. Takahashi, H. Yamada, S. Omura, : In vitro antitrypanosomal activity of 12 low-molecular-weight antibiotics and observations of structure/activity relationships,J. Antibiot.,63,619-622(2010)
  5. K. Otoguro, A. Ishiyama, M. Iwatsuki, M. Namatame, A. Nishihara-Tukashima, T. Nakashima, S. Shibahara, S. Kondo, H. Yamada, S. Omura, : In vitro and in vivo anti- Trypanosoma brucei activities of phenazinomycin and related compounds,J. Antibiot.,63,579-581(2010)
  6. J. Hashida, M. Niitsuma, M. Iwatsuki, M. Mori, A. Ishiyama, M. Namatame, A. Nishihara-Tsukashima, K. Nonaka, H. Ui, R. Masuma, K. Otoguro, H. Yamada, K. Shiomi, S. Omura, : Pyrenocine I, a new pyrenocine analog produced by Paecilomyces sp. FKI-3573,J. Antibiot.,63,559-561(2010)
  7. K. Otoguro, M. Iwatsuki, A. Ishiyama, M. Namatame, A. Nishihara-Tukashima, S. Shibahara, S. Kondo, H. Yamada, S. Omura, : Promising lead compounds for novel antiprotozoals,J. Antibiot.,63,381-384(2010)
  8. M. Iwatsuki, Y. Kinoshita, M. Niitsuma, J. Hashida, M. Mori, A. Ishiyama, M. Namatame, A. Nishihara-Tsukashima, K. Nonaka, R. Masuma, K. Otoguro, H. Yamada, K. Shiomi, S. Omura, : Antitrypanosomal peptaibiotics, trichosporins B-VIIa and B-VIIb, produced by Trichoderma polysporum FKI-4452,J. Antibiot.,63,331-333(2010)
  9. A. Ishiyama, M. Iwatsuki, M. Namatame, A. Nishihara-Tsukashima, T. Sunazuka, Y. Takahashi, S. Omura, K. Otoguro, : Borrelidin, a potent antimalarial: stage-specific inhibition profile of synchronized cultures of Plasmodium falciparum,J. Antibiot.,64,381-384(2011)
  10. K. Kimura, M. Iwatsuki, T. Nagai, A. Matsumoto, Y. Takahashi, K. Shiomi, S. Omura, : A small-molecule inhibitor of the bacterial type III secretion system protects against in vivoinfection with Citrobacter rodentium, J. Antibiot.,64,197-203(2011)
  11. S. Ikeda, H. Hanaki, C. Yanagisawa, Y. Ikeda-Dantsuji, H. Matsui, M. Iwatsuki, K. Shiomi, T. Nakae, K. Sunakawa, S. Omura, : Identification of the active component that induces vancomycin resistance in MRSA,J. Antibiot.,63,533-538(2010)
  12. K. Otoguro, M. Iwatsuki, A. Ishiyama, M. Namatame, A. Nishihara-Tsukashima, S. Sato, M. Hatsu, H. Iinuma, S. Shibahara, S. Nimura, S. Kondo, H. Yamada, S. Omura, : In vitro and in vivo antiprotozoal activities of bispolides and their derivatives,J. Antibiot.,63,275-277(2010)
  13. R. Uchida, M. Iwatsuki, Y.-P. Kim, S. Omura, H. Tomoda, : Nosokomycins, new antibiotics discovered in an in vivo-mimic infection model using silkworm larvae. II: Structure elucidation,J. Antibiot.,63,157-163(2010)
  14. R. Uchida, M. Iwatsuki, Y.-P. Kim, S. Ohte, S. Omura, H. Tomoda, : Nosokomycins, new antibiotics discovered in an in vivo-mimic infection model using silkworm larvae. I: Fermentation, isolation and biological properties,J. Antibiot.,63,151-155(2010)
  15. A.Tsutsui, Y. Furuya, T. Hirose, R. Kim, R. Masuma, A. Matsumoto, Y. Takahashi, A. Ishiyama, M. Namatame, K. Otoguro, S. Omura,T. Sunazuka, : Boromycin derivatives: Synthesis and antimalarial activity in vitro and in vivo,Hetrerocycles,82,289-295(2010)