New Tetromycin Derivatives with Anti-Trypanosomal and Protease Inhibitory Activities

New Tetromycin Derivatives with Anti-Trypanosomal and Protease Inhibitory Activities

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

Four new tetromycin derivatives, tetromycins 1–4 and a previously known one, tetromycin B (5) were isolated from Streptomyces axinellae Pol001T 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 Mpro, and PLpro. The compounds showed antiparasitic activities against T. brucei and time-dependent inhibition of cathepsin L-like proteases with Ki values in the low micromolar range.

2011

tetromycin, anti-trypanosomal, protease inhibition, Streptomyces axinellae, marine sponge

DOI: 10.3390/md9101682

Marine Drugs

MDPI AG

Biology (General)

EN