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


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.

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  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.

  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 

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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.

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Correspondence to Aki Ishiyama or Masato Iwatsuki.

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Kimura, Si., Watanabe, Y., Shibasaki, S. et al. New antimalarial iromycin analogs produced by Streptomyces sp. RBL-0292. J Antibiot 77, 272–277 (2024).

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