Suberitamides A-C, Aryl Alkaloids from a Pseudosuberites sp. Marine Sponge that Inhibit Cbl-b Ubiquitin Ligase Activity

• Published in: Marine drugs 2020-10, Vol.18 (11), p.536
• Main Authors: Kim, Chang-Kwon, Wang, Dongdong, Wilson, Brice A P, Saurí, Josep, Voeller, Donna, Lipkowitz, Stanley, O'Keefe, Barry R, Gustafson, Kirk R
• Format: Article
• Language: English
• Subjects: Alkaloids - isolation & purification; Alkaloids - pharmacology; Animals; Cbl-b ubiquitin ligase inhibition; Enzyme Inhibitors - isolation & purification; Enzyme Inhibitors - pharmacology; marine sponge; Molecular Structure; PIP HSQMBC IPAP; Porifera - metabolism; Proto-Oncogene Proteins c-cbl - antagonists & inhibitors; Proto-Oncogene Proteins c-cbl - metabolism; Pseudosuberites sp; Structure-Activity Relationship; suberitamides
• ISSN: 1660-3397; 1660-3397
• DOI: 10.3390/md18110536

Three new aryl alkaloids named suberitamides A-C ( - ), were isolated from an extract of the marine sponge sp. collected along the coast of North Carolina. Their planar structures were established by extensive nuclear magnetic resonance (NMR) and mass spectrometry (MS) analysis. To assign the challenging relative configuration of the saturated five-membered ring in suberitamide A ( ), a simple and efficient NMR protocol was applied that is based on the analysis of 2- and 3-bond H- C spin-spin coupling constants using a PIP (pure in-phase) HSQMBC (heteronuclear single quantum multiple bond correlation) IPAP (in-phase and anti-phase) experiment. Suberitamides A ( ) and B ( ) inhibited Cbl-b, an E3 ubiquitin ligase that is an important modulator of immune cell function, with IC values of approximately 11 μM.