Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

ABSTRACT: Three new aryl alkaloids named suberitamides A-C (1-3), were isolated from an extract of the marine sponge Pseudosuberites 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 (1), a simple and efficient NMR protocol was applied that is based on the analysis of 2- and 3-bond 1H-13C 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 (1) and B (2) inhibited Cbl-b, an E3 ubiquitin ligase that is an important modulator of immune cell function, with IC50 values of approximately 11 ?M.

SUBMITTER: Kim CK

PROVIDER: S-EPMC7693676 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

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

Kim Chang-Kwon CK Wang Dongdong D Wilson Brice A P BAP Saurí Josep J Voeller Donna D Lipkowitz Stanley S O'Keefe Barry R BR Gustafson Kirk R KR

Marine drugs 20201028 11

Three new aryl alkaloids named suberitamides A-C (1-3), were isolated from an extract of the marine sponge Pseudosuberites 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 (1), a simple and efficient NMR protocol was applied that is based on the ...[more]

PMID: 33126420

Similar Datasets

E3 ubiquitin ligase Cbl-b regulates Pten via Nedd4 in T cells independently of its ubiquitin ligase activity.

Project description:E3 ubiquitin ligase Cbl-b plays a crucial role in T cell activation and tolerance induction. However, the molecular mechanism by which Cbl-b inhibits T cell activation remains unclear. Here, we report that Cbl-b does not inhibit PI3K but rather suppresses TCR/CD28-induced inactivation of Pten. The elevated Akt activity in Cbl-b(-/-) T cells is therefore due to heightened Pten inactivation. Suppression of Pten inactivation in T cells by Cbl-b is achieved by impeding the association of Pten with Nedd4, which targets Pten K13 for K63-linked polyubiquitination. Consistent with this finding, introducing Nedd4 deficiency into Cbl-b(-/-) mice abrogates hyper-T cell responses caused by the loss of Cbl-b. Hence, our data demonstrate that Cbl-b inhibits T cell activation by suppressing Pten inactivation independently of its ubiquitin ligase activity.

| S-EPMC3387815 | biostudies-literature

New Alkaloids and Polyketides from the Marine Sponge-Derived Fungus Penicillium sp. SCSIO41015.

Project description:The sponge-derived fungus Penicillium sp. SCSIO41015 cultured on solid rice medium yielded twenty-one compounds (1-21), including two new alkaloids (1 and 2) and one new pyrone derivative (3). Their structures were elucidated by analysis of 1D/2D NMR data and HR-ESI-MS. Their absolute configurations were established by single-crystal X-ray diffraction analysis and comparison of the experimental with reported specific rotation values. Compound 16 exhibited selective cytotoxic activity against the human gastric cancer cells MGC803, with IC50 value of 5.19 μM. Compounds 9 and 18 showed weak antibacterial activity against Staphylococcus aureus and Acinetobacter baumannii, respectively, both with MIC values of 57 μg/mL. Furthermore, compound 16 displayed potent antibacterial activity against S. aureus with an MIC value of 3.75 μg/mL.

| S-EPMC6669684 | biostudies-literature

New 2-Methoxy Acetylenic Acids and Pyrazole Alkaloids from the Marine Sponge Cinachyrella sp.

Project description:Three new 2-methoxy acetylenic acids (1-3) and a known derivative (4), in addition to three new natural pyrazole alkaloids (5-7) were isolated from an Indonesian marine sponge of the genus Cinachyrella. Compounds 5 and 6 have previously been reported as synthetic compounds. The structures of the new compounds were established on the basis of one- and two-dimensional NMR spectroscopy as well as by mass spectrometric data. The absolute configuration of the new acetylenic acid derivatives (1-3) was established by ECD spectroscopy. All isolated compounds were evaluated for their cytotoxicity against L5178Y mouse lymphoma cells. Compounds 1-4 exhibited strong activity with an IC50 value of 0.3 µM. A plausible biosynthetic pathway for the pyrazole metabolites 5-7 is proposed.

| S-EPMC5706045 | biostudies-literature

Ceratinadins E and F, New Bromotyrosine Alkaloids from an Okinawan Marine Sponge Pseudoceratina sp.

Project description:Two new bromotyrosine alkaloids, ceratinadins E (1) and F (2), were isolated from an Okinawan marine sponge Pseudoceratina sp. as well as a known bromotyrosine alkaloid, psammaplysin F (3). The gross structures of 1 and 2 were elucidated on the basis of spectroscopic data. The absolute configurations of 1 and 2 were assigned by comparison of the NMR and ECD data with those of a known related bromotyrosine alkaloid, psammaplysin A (4). Ceratinadins E (1) and F (2) are new bromotyrosine alkaloids possessing an 8,10-dibromo-9-methoxy-1,6-dioxa-2-azaspiro[4.6]undeca-2,7,9-trien-4-ol unit with two or three 11-N-methylmoloka'iamine units connected by carbonyl groups, respectively. Ceratinadin E (1) exhibited antimalarial activities against a drug-resistant and a drug-sensitive strains of Plasmodium falciparum (K1 and FCR3 strains, respectively).

| S-EPMC6316200 | biostudies-literature

Discovery of new pyridoacridine alkaloids from Lissoclinum cf. badium that inhibit the ubiquitin ligase activity of Hdm2 and stabilize p53.

Project description:Compounds that stabilize p53 could suppress tumors providing a additional tool to fight cancer. Mdm2, and the human ortholog, Hdm2 serve as ubiquitin E3 ligases and target p53 for ubiquitylation and degradation. Inhibition of Hdm2 stabilizes p53, inhibits cell proliferation and induces apoptosis. Using HTS to discover inhibitors, we identified three new alkaloids, isolissoclinotoxin B, diplamine B, and lissoclinidine B from Lissoclinum cf. badium. Lissoclinidine B inhibited ubiquitylation and degradation of p53, and selectively killed transformed cells harboring wild-type p53, suggesting this compound could be used to develop new treatments.

| S-EPMC2718708 | biostudies-literature

Steroidal alkaloids from the marine sponge Corticium niger that inhibit growth of human colon carcinoma cells.

Project description:Bioinformatic analysis of data from the NCI-60 cell cytotoxicity screen revealed a subset of extracts that showed selective cytotoxic activity toward human colon carcinoma cell lines. Bioassay-guided fractionation of a colon cancer selective extract from a Philippines collection of the marine sponge Corticium niger provided two new steroidal alkaloids, plakinamines N (1) and O (2), along with two known compounds of the plakinamine class (3, 4). The structures of these compounds were elucidated by interpretation of combined MS and NMR spectroscopic data. Plakinamines N (1), O (2), and J (4) were tested for antiproliferative activity in the NCI-60 screen, and they showed enhanced inhibitory effects against all of the colon cell lines with mean GI50 values of 11.5, 2.4, and 1.4 ?M, respectively.

| S-EPMC4251534 | biostudies-literature

Marine sponge Hymeniacidon sp. amphilectane metabolites potently inhibit rat brain microglia thromboxane B2 generation.

Project description:The effects of five Hymeniacidon sp. amphilectane metabolites (1-5) and two semi-synthetic analogs (6 and 7) on thromboxane B(2) (TXB(2)) and superoxide anion (O(2)(-)) generation from Escherichia coli LPS-activated rat brain microglia were investigated. All Hymeniacidon sp. metabolites and analogs potently inhibited TXB(2) (IC(50)=0.20-4.69?M) with low lactate dehydrogenase release and minimal mitochondrial dehydrogenase inhibition. While a lack of O(2)(-) inhibition would suggest that Hymeniacidon sp. metabolites and derivatives inhibit TXB(2) synthesis by a cyclooxygenase-dependent mechanism, their pharmacologic potency and limited in vitro cytotoxicity warrants further investigation to develop them as lead compounds to modulate enhanced TBX(2) release by activated microglia in neuroinflammatory disorders.

| S-EPMC3272584 | biostudies-literature

Itch WW Domains Inhibit Its E3 Ubiquitin Ligase Activity by Blocking E2-E3 Ligase Trans-thiolation.

Project description:Nedd4-family E3 ubiquitin ligases regulate an array of biologic processes. Autoinhibition maintains these catalytic ligases in an inactive state through several mechanisms. However, although some Nedd4 family members are activated by binding to Nedd4 family-interacting proteins (Ndfips), how binding activates E3 function remains unclear. Our data reveal how these two regulatory processes are linked functionally. In the absence of Ndfip1, the Nedd4 family member Itch can bind an E2 but cannot accept ubiquitin onto its catalytic cysteine. This is because Itch is autoinhibited by an intramolecular interaction between its HECT (homologous to the E6-AP carboxy terminus domain) and two central WW domains. Ndfip1 binds these WW domains to release the HECT, allowing trans-thiolation and Itch catalytic activity. This molecular switch also regulates the closely related family member WWP2. Importantly, multiple PY motifs are required for Ndfip1 to activate Itch, functionally distinguishing Ndfips from single PY-containing substrates. These data establish a novel mechanism for control of the function of a subfamily of Nedd4 E3 ligases at the level of E2-E3 trans-thiolation.

| S-EPMC4583040 | biostudies-literature

Phosphorylation control of the ubiquitin ligase Cbl is conserved in choanoflagellates.

Project description:Cbl proteins are E3 ubiquitin ligases specialized for the regulation of tyrosine kinases by ubiquitylation. Human Cbl proteins are activated by tyrosine phosphorylation, thus setting up a feedback loop whereby the activation of tyrosine kinases triggers their own degradation. Cbl proteins are targeted to their substrates by a phosphotyrosine-binding SH2 domain. Choanoflagellates, unicellular eukaryotes that are closely related to metazoans, also contain Cbl. The tyrosine kinase complement of choanoflagellates is distinct from that of metazoans, and it is unclear if choanoflagellate Cbl is regulated similarly to metazoan Cbl. Here, we performed structure-function studies on Cbl from the choanoflagellate species Salpingoeca rosetta and found that it undergoes phosphorylation-dependent activation. We show that S. rosetta Cbl can be phosphorylated by S. rosetta Src kinase, and that it can ubiquitylate S. rosetta Src. We also compared the substrate selectivity of human and S. rosetta Cbl by measuring ubiquitylation of Src constructs in which Cbl-recruitment sites are placed in different contexts with respect to the kinase domain. Our results indicate that for both human and S. rosetta Cbl, ubiquitylation depends on proximity and accessibility, rather than being targeted toward specific lysine residues. Our results point to an ancient interplay between phosphotyrosine and ubiquitin signaling in the metazoan lineage.

| S-EPMC5916117 | biostudies-literature

Bioactive Bis(indole) Alkaloids from a Spongosorites sp. Sponge.

Project description:Six new bis(indole) alkaloids (1-6) along with eight known ones of the topsentin class were isolated from a Spongosorites sp. sponge of Korea. Based on the results of combined spectroscopic analyses, the structures of spongosoritins A-D (1-4) were determined to possess a 2-methoxy-1-imidazole-5-one core connecting the indole moieties, and these were linked by a linear urea bridge for spongocarbamides A (5) and B (6). The absolute configurations of spongosoritins were assigned by electronic circular dichroism (ECD) computation. The new compounds exhibited moderate inhibition against transpeptidase sortase A and weak inhibition against human pathogenic bacteria and A549 and K562 cancer cell lines.

| S-EPMC7824209 | biostudies-literature