Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2011;9(10):1682-1697.
doi: 10.3390/md9101682. Epub 2011 Sep 26.

New tetromycin derivatives with anti-trypanosomal and protease inhibitory activities

Sheila M Pimentel-Elardo  1 , Verena Buback  2 , Tobias A M Gulder  3 , Tim S Bugni  4 , Jason Reppart  4 , Gerhard Bringmann  3 , Chris M Ireland  4 , Tanja Schirmeister  2 , Ute Hentschel  1
Affiliations

New tetromycin derivatives with anti-trypanosomal and protease inhibitory activities

Sheila M Pimentel-Elardo et al. Mar Drugs. 2011.

Abstract

Four new tetromycin derivatives, tetromycins 1-4 and a previously known one, tetromycin B (5) were isolated from Streptomyces axinellae Pol001(T) cultivated from the Mediterranean sponge Axinella polypoides. Structures were assigned using extensive 1D and 2D NMR spectroscopy as well as HRESIMS analysis. The compounds were tested for antiparasitic activities against Leishmania major and Trypanosoma brucei, and for protease inhibition against several cysteine proteases such as falcipain, rhodesain, cathepsin L, cathepsin B, and viral proteases SARS-CoV M(pro), and PL(pro). The compounds showed antiparasitic activities against T. brucei and time-dependent inhibition of cathepsin L-like proteases with K(i) values in the low micromolar range.

Keywords: Streptomyces axinellae; anti-trypanosomal; marine sponge; protease inhibition; tetromycin.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Selected 2D NMR correlations in tetromycin 4.
Figure 2
Figure 2
Selected 2D NMR correlations in decalin of tetromycin 4.
Figure 3
Figure 3
Selected 2D NMR correlations in decalin of tetromycin 3.
Figure 4
Figure 4
Selected 2D NMR correlations in the cyclohexene fragment of tetromycin 4.
Figure 5
Figure 5
Structures of tetromycins 1–4 and tetromycin B (5).
Figure 5
Figure 5
Structures of tetromycins 1–4 and tetromycin B (5).
Figure 6
Figure 6
Inhibition of rhodesain (left, time-dependent inhibition) and cathepsin B (right, non-time dependent inhibition) by tetromycin B (5) (inhibitor concentrations from top to bottom: 0, 1.67, 3.34, 6.68, 8.35, 10.0, 13.4, 16.7 μM).
Figure 7
Figure 7
Inhibition of cathepsin B by tetromycin B (5). A Ki value of 1.50 μM was obtained.
Figure 8
Figure 8
Inhibition of rhodesain by compound 3; data from two independent assays are shown. The following inhibition constants were obtained: Ki = 2.1 μM; ki = 0.042 min−1; k2nd = 38,100 M−1 min−1.
See this image and copyright information in PMC

References

    1. Peiris JS, Yuen KY, Osterhaus AD, Stohr K. The severe acute respiratory syndrome. N. Engl. J. Med. 2003;349:243–2441. - PubMed
    1. Fear G, Komarnytsky S, Raskin I. Protease inhibitors and their peptidomimetic derivatives as potential drugs. Pharmacol. Ther. 2007;113:354–368. - PMC - PubMed
    1. Anand K, Ziebuhr J, Wadhwani P, Mesters JR, Hilgenfeld R. Coronavirus main proteinase (3CLpro) structure: Basis for design of anti-SARS drugs. Science. 2003;300:1763–1767. - PubMed
    1. Laport MS, Santos OS, Muricy G. Marine sponges: Potential sources of new antimicrobial drugs. Curr. Pharm. Biotechnol. 2009;10:86–105. - PubMed
    1. Scheuermayer M, Pimentel-Elardo S, Fieseler L, Grozdanov L, Hentschel U. Microorganisms of Sponges: Phylogenetic Diversity and Biotechnological Potential. In: Proksch P, Müller WEG, editors. Frontiers in Marine Biotechnology. Horizon Bioscience; Norwich, UK: 2006. pp. 289–312.

Publication types

MeSH terms

LinkOut - more resources