Abstract
We have screened microbial culture filtrates for nitrogen monoxide (NO) production inhibitors using mouse macrophage cell line RAW264.7. As a result, paxilline, 21-isopentenylpaxilline and a novel analog of paxilline have been isolated from the culture filtrate of fungus Eupenicillium shearii. The novel analog possesses an additional dihydropyran ring, and was named as pyrapaxilline. This compound inhibited the NO production with lower toxicity than paxilline.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Korhonen, R., Lahti, A., Kankaanranta, H. & Moilanen, E. Nitric oxide production and signaling in inflammation. Curr Drug Targets Inflamm Allergy 4, 471–479 (2005).
Ariga, A., Namekawa, J., Matsumoto, N., Inoue, J. & Umezawa, K. Inhibition of tumor necrosis factor-alpha-induced nuclear translocation and activation of NF-kappa B by dehydroxymethylepoxyquinomicin. J. Biol. Chem. 277, 24625–24630 (2002).
Suzuki, Y., Sugiyama, C., Ohno, O. & Umezawa, K. Preparation and biological activities of optically active dehydroxymethylepoxyquinomicin, a novel NF-κB inhibitor. Tetrahedron 60, 7061–7066 (2004).
Umezawa, K. Inhibition of tumor growth by NF-κB inhibitors. Cancer Sci. 97, 990–995 (2006).
Wang, Z., Igarashi, M., Ikeda, Y., Horie, R. & Umezawa, K. Inhibition of NF-kappa B activation by 9-methylstreptimidone isolated from Streptomyces. Heterocycles 69, 377–383 (2006).
Tachibana, M., Matsui, C., Takeuchi, Y., Suzuki, E. & Umezawa, K. Inhibition of NF-κB activation by penicillic acid and dihydropenicillic acid isolated from fungi. Heterocycles 76, 1561–1569 (2008).
Springer, J. P., Clardy, J., Wells, J. M., Cole, R. J. & Kirksey, J. W. The structure of paxilline, a tremorgenic metabolite of Penicillium paxilli Bainier. Tetrahedron Lett. 16, 2531–2534 (1975).
Belofsky, G. N., Gloer, J. B., Wicklow, D. T. & Dowd, P. F. Antiinsectan alkaloids: Shearinines A-C and a new paxilline derivative from the ascostromata of Eupenicillium shearii. Tetrahedron 51, 3959–3968 (1995).
Singh, S. B. et al. Nodulisporic acids D-F: structure, biological activities, and biogenetic relationships. J. Nat. Prod. 67, 1496–1506 (2004).
Wilkins, A. L. et al. Structure elucidation of janthitrem B, a tremorgenic metabolite of Penicillium janthinellum, and relative configuration of the A and B rings of janthitrems B, E, and F. J. Agric. Food Chem. 40, 1307–1309 (1992).
Xu, M. et al. Shearinines D-K, new indole triterpenoids from an endophytic Penicillium sp. (strain HKI0459) with blocking activity on large-conductance calcium-activated potassium channels. Tetrahedron 63, 435–444 (2007).
Knaus, H. G. et al. Tremorgenic indole alkaloids potently inhibit smooth muscle high-conductance calcium-activated potassium channels. Biochemistry 33, 5819–5828 (1994).
Papavlassopoulos, M. et al. MaxiK blockade selectively inhibits the lipopolysaccharide-induced I kappa B-alpha/NF-kappa B signaling pathway in macrophages. J. Immunol. 177, 4086–4093 (2006).
Goetz, M. A. et al. (Merck & Co. Inc.). Novel maxi-k channel blockers, methods of use and process for making the same. WO 03/105868, 24 December (2003).
Dubois, R. N. et al. Cyclooxygenase in biology and disease. FASEB J 12, 1063–1073 (1998).
Acknowledgements
We thank Dr Shinichi Kondo, Bioscience Associates, Tokyo, for his valuable suggestions.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no conflict of interest.
Rights and permissions
About this article
Cite this article
Matsui, C., Ikeda, Y., Iinuma, H. et al. Isolation of a novel paxilline analog pyrapaxilline from fungus that inhibits LPS-induced NO production. J Antibiot 67, 787–790 (2014). https://doi.org/10.1038/ja.2014.63
Received:
Revised:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/ja.2014.63
This article is cited by
-
The chemical structures and biological activities of indole diterpenoids
Natural Products and Bioprospecting (2023)
-
Inhibition of cellular inflammatory mediator production and amelioration of learning deficit in flies by deep sea Aspergillus-derived cyclopenin
The Journal of Antibiotics (2020)
-
Novel p-terphenyl glycoside with a rare 2,6-dideoxyhexopyranose moiety from Actinomycete strain SF2911 that inhibits cancer cell migration
The Journal of Antibiotics (2017)
