Swinhopeptolides A and B: Cyclic Depsipeptides from the Sponge Theonella swinhoei That Inhibit Ras/Raf Interaction
| Autor: | Curtis J. Henrich, Emily A. Smith, Carole A. Bewley, Chang-Kwon Kim, Kirk R. Gustafson, Deborah K. Morrison, Dongdong Wang, David E. Durrant, Richard W. Fuller, Heidi R. Bokesch |
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| Rok vydání: | 2020 |
| Předmět: |
Stereochemistry
Pharmaceutical Science Article Analytical Chemistry Serine Papua New Guinea Residue (chemistry) Polyketide Depsipeptides Drug Discovery Animals Moiety Proline Amino Acids Nuclear Magnetic Resonance Biomolecular Conformational isomerism Pharmacology Depsipeptide Molecular Structure biology Chemistry Organic Chemistry biology.organism_classification Porifera Proto-Oncogene Proteins c-raf Sponge Complementary and alternative medicine ras Proteins Molecular Medicine Theonella Signal Transduction |
| Zdroj: | J Nat Prod |
| ISSN: | 1520-6025 0163-3864 |
| DOI: | 10.1021/acs.jnatprod.0c00136 |
| Popis: | Two new cyclic depsipeptides named swinhopeptolides A (1) and B (2), have been isolated from the marine sponge Theonella swinhoei cf. verrucosa, collected from Papua New Guinea. They each contain 11 diverse amino acid resudues and 13-carbon polyketide moieties attached at the N-terminus. Compounds 1 and 2 each exist as two conformers in DMSO-d(6) due to cis/trans isomerism of the proline residue, and their structures were successfully assigned by extensive NMR analyses complemented by chemical degradation and derivatization studies. Swinhopeptolide B (2) contains a previously undescribed 2,6,8-trimethyldeca-(2E,4E,6E)-trienoic acid moiety N-linked to a terminal serine residue. Swinhopeptolides A (1) and B (2) showed significant inhibition of the Ras/Raf signaling pathway with IC(50) values of 5.8 and 8.5 μM, respectively. |
| Databáze: | OpenAIRE |
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