Serveur d'exploration SRAS

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New Tetromycin Derivatives with Anti-Trypanosomal and Protease Inhibitory Activities †

Identifieur interne : 002100 ( Main/Merge ); précédent : 002099; suivant : 002101

New Tetromycin Derivatives with Anti-Trypanosomal and Protease Inhibitory Activities †

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

Source :

RBID : PMC:3210601

Descripteurs français

English descriptors

Abstract

Four new tetromycin derivatives, tetromycins 14 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.


Url:
DOI: 10.3390/md9101682
PubMed: 22072992
PubMed Central: 3210601

Links toward previous steps (curation, corpus...)


Links to Exploration step

PMC:3210601

Le document en format XML

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<email>tbugni@pharmacy.wisc.edu</email>
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<email>jreppart@gmail.com</email>
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<affiliation>
<nlm:aff id="af4-marinedrugs-09-01682">Department of Medicinal Chemistry, University of Utah, Salt Lake City, UT 84112, USA; E-Mails:
<email>tbugni@pharmacy.wisc.edu</email>
(T.S.B.);
<email>jreppart@gmail.com</email>
(J.R.);
<email>cireland@pharm.utah.edu</email>
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<email>verena.buback@uni-wuerzburg.de</email>
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<email>schirmei@pharmazie.uni-wuerzburg.de</email>
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<email>ute.hentschel@uni-wuerzburg.de</email>
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<term>Axinella (microbiology)</term>
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<term>Inhibiteurs de protéases (pharmacologie)</term>
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<term>Trypanocidal Agents</term>
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<term>Streptomyces</term>
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<front>
<div type="abstract" xml:lang="en">
<p>Four new tetromycin derivatives, tetromycins
<bold>1</bold>
<bold>4</bold>
and a previously known one, tetromycin B (
<bold>5</bold>
) were isolated from
<italic>Streptomyces axinellae</italic>
Pol001
<sup>T</sup>
cultivated from the Mediterranean sponge
<italic>Axinella polypoides</italic>
. Structures were assigned using extensive 1D and 2D NMR spectroscopy as well as HRESIMS analysis. The compounds were tested for antiparasitic activities against
<italic>Leishmania major</italic>
and
<italic>Trypanosoma brucei</italic>
, and for protease inhibition against several cysteine proteases such as falcipain, rhodesain, cathepsin L, cathepsin B, and viral proteases SARS-CoV M
<sup>pro</sup>
, and PL
<sup>pro</sup>
. The compounds showed antiparasitic activities against
<italic>T. brucei</italic>
and time-dependent inhibition of cathepsin L-like proteases with
<italic>K</italic>
<sub>i</sub>
values in the low micromolar range.</p>
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