Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

New antimalarial iromycin analogs produced by Streptomyces sp. RBL-0292

The Journal of Antibiotics volume 77, pages 272–277 (2024)Cite this article

Subjects

Abstract

Two new antimalarial compounds, named prenylpyridones A (1) and B (2), were discovered from the actinomycete cultured material of Streptomyces sp. RBL-0292 isolated from the soil on Hamahiga Island in Okinawa prefecture. The structures of 1 and 2 were elucidated as new iromycin analogs having α-pyridone ring by MS and NMR analyses. Compounds 1 and 2 showed moderate in vitro antimalarial activity against chloroquine-sensitive and chloroquine-resistant Plasmodium falciparum strains, with IC50 values ranging from 80.7 to 106.7 µM.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Scheme 1
Fig. 2

Similar content being viewed by others

References

  1. Miller LH, Baruch DI, Marsh K, Doumbo OK. The pathogenic basis of malaria. Nature. 2002;415:673–9.

    Article  CAS  PubMed  Google Scholar 

  2. World Health Organization, World Malaria Report 2022. https://www.who.int/teams/global-malaria-programme/reports/world-malaria-report-2022

  3. Ashley EA, Pyae Phyo A, Woodrow CJ. Malaria. Lancet. 2018;391:1608–21.

    Article  PubMed  Google Scholar 

  4. Hayashi Y, Fukasawa W, Hirose T, Iwatsuki M, Hokari R, Ishiyama A, et al. Kozupeptins, antimalarial agents produced by Paracamarosporium species: Isolation, structural elucidation, total synthesis, and bioactivity. Org Lett. 2019;21:2180–4.

    Article  CAS  PubMed  Google Scholar 

  5. Ishiyama A, Hokari R, Nonaka K, Chiba T, Miura H, Otoguro K, et al. Diatretol, an α, α’-dioxo-diketopiperazine, is a potent in vitro and in vivo antimalarial. J Antibiot. 2021;74:266–8.

    Article  CAS  Google Scholar 

  6. Ouchi T, Watanabe Y, Nonaka K, Muramatsu R, Noguchi C, Tozawa M, et al. Clonocoprogens A, B and C, new antimalarial coprogens from the Okinawan fungus Clonostachys compactiuscula FKR-0021. J Antibiot. 2020;73:365–71.

    Article  CAS  Google Scholar 

  7. Watanabe Y, Hachiya K, Ikeda A, Nonaka K, Higo M, Muramatsu R, et al. Koshidacins A and B, antiplasmodial cyclic tetrapeptides from the Okinawan fungus Pochonia boninensis FKR-0564. J Nat Prod. 2022;85:2641–9.

    Article  CAS  PubMed  Google Scholar 

  8. Watanabe Y, Arakawa E, Kondo N, Nonaka K, Ikeda A, Hirose T, et al. New antimalarial fusarochromanone analogs produced by the fungal strain Fusarium sp. FKI-9521. J Antibiot. 2023;76:384–91.

    Article  CAS  Google Scholar 

  9. Inahashi Y, Matsumoto A, Danbara H, Ōmura S, Takahashi Y. Phytohabitans suffuscus gen. nov., sp. nov., an actinomycete of the family Micromonosporaceae isolated from plant roots. Int J Syst Evol Microbiol. 2010;60:2652–8.

    Article  CAS  PubMed  Google Scholar 

  10. Yoon SH, Ha SM, Kwon S, Lim J, Kim Y, Seo H, et al. Introducing EzBioCloud: a taxonomically united database of 16S rRNA gene sequences and whole-genome assemblies. Int J Syst Evol Microbiol. 2017;67:1613–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Otoguro K, Ui H, Ishiyama A, Arai N, Kobayashi M, Takahashi Y, et al. In vitro antimalarial activities of the microbial metabolites. J Antibiot. 2003;56:322–4.

    Article  Google Scholar 

  12. Otoguro K, Kohana A, Manabe C, Ishiyama A, Ui H, Shiomi K, et al. Potent antimalarial activities of polyether antibiotic, X-206. J Antibiot. 2001;54:658–63.

    Article  CAS  Google Scholar 

  13. Surup F, Wagner O, von Frieling J, Schleicher M, Oess S, Müller P, et al. The iromycins, a new family of pyridone metabolites from Streptomyces sp. I. Structure, NOS inhibitory activity, and biosynthesis. J Org Chem. 2007;72:5085–90.

    Article  CAS  PubMed  Google Scholar 

  14. Surup F, Shojaei H, von Zezschwitz P, Kunze B, Grond S. Iromycins from Streptomyces sp. and from synthesis: New inhibitors of the mitochondrial electron transport chain. Bioorg Med Chem. 2008;16:1738–46.

    Article  CAS  PubMed  Google Scholar 

  15. Sukenaga Y, Yamazaki T, Aoyama T, Takayasu Y, Harada T. JP1997-55460, 1997.

  16. Ostera G, Tokumasu F, Oliveira F, Sa J, Furuya T, Teixeira C, et al. Plasmodium falciparum: food vacuole localization of nitric oxide-derived species in intraerythrocytic stages of the malaria parasite. Exp Parasitol. 2008;120:29–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Ghigo D, Todde R, Ginsburg H, Costamagna C, Gautret P, Bussolino F, et al. Erythrocyte stages of Plasmodium falciparum exhibit a high nitric oxide synthase (NOS) activity and release an NOS-inducing soluble factor. J Exp Med. 1995;182:677–88.

    Article  CAS  PubMed  Google Scholar 

  18. Hempel C, Kohnke H, Maretty L, Jensen PØ, Staalsø T, Kurtzhals JAL. Plasmodium falciparum avoids change in erythrocytic surface expression of phagocytosis markers during inhibition of nitric oxide synthase activity. Mol Biochem Parasitol. 2014;198:29–36.

    Article  CAS  PubMed  Google Scholar 

  19. Schnermann MJ, Romero FA, Hwang I, Nakamaru-Ogiso E, Yagi T, Boger DL. Total synthesis of piericidin A1 and B1 and key analogues. J Am Chem Soc. 2006;128:11799–807.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Ui H, Shiomi K, Suzuki H, Hatano H, Morimoto H, Yamaguchi Y, et al. Verticipyrone, a new NADH-fumarate reductase inhibitor, produced by Verticillium sp. FKI-1083. J Antibiot. 2006;59:785–90.

    Article  CAS  Google Scholar 

  21. Ke H, Ganesan SM, Dass S, Morrisey JM, Pou S, Nilsen A, et al. Mitochondrial type II NADH dehydrogenase of Plasmodium falciparum (PfNDH2) is dispensable in the asexual blood stages. PLoS One. 2019;14:e0214023.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We are grateful to Distinguished Emeritus Professor Satoshi Ōmura (Kitasato University) for his helpful support and valuable guidance and suggestions. We thank Dr. Kenichiro Nagai, Ms. Reiko Seki, and Ms. Noriko Sato (School of Pharmacy, Kitasato University) for various instrumental analyses. We thank Dr. Marcel Kaiser and the Parasite Chemotherapy Unit at Swiss TPH, Allschwil, Switzerland for helping in establishing the in vivo safety model. This research was partially supported by Platform Project for Supporting Drug Discovery and Life Science Research (Basis for Supporting Innovative Drug Discovery and Life Science Research (BINDS)) from AMED under Grant Number JP21am0101096 (Phase I) and JP22ama121035 (Phase II). This work was supported by JSPS KAKENHI Grant Numbers JP20K07106 and JP23H04887.

Author information

Author notes

  1. These authors contributed equally: So-ichiro Kimura, Yoshihiro Watanabe

Authors and Affiliations

  1. Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan

    So-ichiro Kimura, Yoshihiro Watanabe, Yuki Inahashi, Toshiaki Sunazuka, Rei Hokari, Aki Ishiyama & Masato Iwatsuki

  2. Ōmura Satoshi Memorial Institute, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan

    Yoshihiro Watanabe, Shiori Shibasaki, Yuki Inahashi, Toshiaki Sunazuka, Rei Hokari, Aki Ishiyama & Masato Iwatsuki

  3. Tropical Biosphere Research Center, University of the Ryukyus, Senbaru 1, Nishihara-cho, Nakagami-gun, Okinawa, 903-0213, Japan

    Naoya Shinzato

Authors
  1. So-ichiro Kimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yoshihiro Watanabe
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shiori Shibasaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Naoya Shinzato
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yuki Inahashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Toshiaki Sunazuka
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Rei Hokari
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Aki Ishiyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Masato Iwatsuki
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Aki Ishiyama or Masato Iwatsuki.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kimura, Si., Watanabe, Y., Shibasaki, S. et al. New antimalarial iromycin analogs produced by Streptomyces sp. RBL-0292. J Antibiot 77, 272–277 (2024). https://doi.org/10.1038/s41429-024-00707-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41429-024-00707-5

Search

Advanced search

Quick links