ABSTRACT
Six new polyoxygenated steroids (1-6) along with clathriol (7) were isolated from the Korean marine sponge Clathria gombawuiensis. Based upon the results of combined spectroscopic analyses, the structures of gombasterols A-F (1-6) were elucidated to be those of highly oxygenated steroids possessing a 3ß,4α,6α,7ß-tetrahydroxy or equivalent (7ß-sodium O-sulfonato for 3) substitution pattern and a C-15 keto group as common structural motifs. The relative and absolute configurations of these steroids, including the rare 14ß configuration of 1-4, were determined by a combination of NOESY, J-based analyses, the 2-methoxy-2-(trifluoromethyl)phenylacetic acid (MTPA) method, and X-ray crystallographic analysis. The absolute configuration of 7 was also assigned by these methods. These compounds moderately enhanced 2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-d-glucose (2-NBDG) uptake in differentiated 3T3-L1 adipocytes and phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) in differentiated mouse C2C12 skeletal myoblasts.
Subject(s)
Porifera/chemistry , Steroids/chemistry , 3T3-L1 Cells , AMP-Activated Protein Kinases/metabolism , Acetyl-CoA Carboxylase/metabolism , Adipocytes/drug effects , Adipocytes/metabolism , Animals , Cell Line , Mice , Myoblasts/drug effects , Myoblasts/metabolism , Phosphorylation/drug effects , Steroids/pharmacologyABSTRACT
Many factors regulate the expression of specialised secondary metabolite biosynthetic gene clusters, which have been recognised as important for the discovery of novel microbial natural products. A cosmid library based on genomic DNA of the marine-derived Streptomyces puniceus Act1085 was constructed and screened to identify a short gene cluster similar to the nonactin biosynthetic cluster. The ORFs of the gene cluster isolated had high amino acid sequence identity, from 82% to 96%, with corresponding ORFs of the nonactin biosynthetic gene cluster from S. griseus subsp. griseus ETH A7796. Despite the expectation that nonactin or its derivatives would be made from heterologous expression of the gene cluster found in S. albus J1074, nocardamine was isolated. The heterologous expression data indicate that the production of nocardamine in S. albus J1074 is due to an ortholog of nonG, a TetR family transcriptional regulator, from S. puniceus Act1085.
Subject(s)
Biosynthetic Pathways , Genes, Bacterial , Multigene Family , Peptides, Cyclic/metabolism , Streptomyces/genetics , Cloning, Molecular , Gene Expression , Macrolides/metabolism , Peptides, Cyclic/genetics , Streptomyces/metabolismABSTRACT
Callyazepin (1) and (3R)-methylazacyclodecane (2), nitrogenous macrocycles, were isolated from a tropical Callyspongia sp. sponge. The combined spectroscopic analyses revealed that the structure of 1 is a bicyclic azepane ammonium salt of a novel structural class derived from mixed biogenetic origins. The configuration of the whole molecule and the conformation of the formamide group were assigned by proton-proton coupling constants, a NOESY analysis, and the application of the phenylglycine methyl ester method. The structure of 2 was identified using combined spectroscopic analyses and ECD measurements. These compounds exhibited moderate cytotoxic activities against the K562 and A549 cell lines.
Subject(s)
Antineoplastic Agents/isolation & purification , Callyspongia/chemistry , Macrocyclic Compounds/isolation & purification , Nitrogen/chemistry , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Drug Screening Assays, Antitumor , Humans , K562 Cells , Macrocyclic Compounds/chemistry , Macrocyclic Compounds/pharmacology , Micronesia , Molecular Conformation , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Oceans and SeasABSTRACT
Six new meroterpenoids (1-6), along with arenarol (7), a known rearranged drimane sesquiterpene hydroquinone, were isolated from a Dysidea sp. sponge collected from the Federated States of Micronesia. On the basis of the results of combined spectroscopic analysis, compound 1 was determined to be the cyclic ether derivative of 7, whereas 2 and 3 were assigned as the corresponding sesquiterpene quinones containing taurine-derived substituents. Compounds 4-6 possess a novel tetracyclic skeleton formed by a direct linkage between the quinone and sesquiterpene moieties. The configurations of these new compounds were assigned on the basis of combined NOESY and ECD analysis. These compounds exhibited cytotoxic and antimicrobial activities and weak inhibition against Na(+)/K(+)-ATPase.
Subject(s)
Cytotoxins/isolation & purification , Dysidea/chemistry , Sesquiterpenes/isolation & purification , Terpenes/isolation & purification , Animals , Cytotoxins/chemistry , Cytotoxins/pharmacology , Humans , K562 Cells , Micronesia , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Sesquiterpenes/chemistry , Sesquiterpenes/pharmacology , Sodium-Potassium-Exchanging ATPase/antagonists & inhibitors , Terpenes/chemistryABSTRACT
Three new terpene metabolites (1-3) were isolated from the marine sponge Clathria gombawuiensis collected from Korean waters. On the basis of the results of combined spectroscopic analyses, the structures of phorone B (1) and ansellone C (2) were determined to be the sesterterpenes of the phorone and ansellone classes, respectively, whereas the saponin gombaside A (3) was a nortriterpene sodium O-sulfonato-glucuronide of the rare 4,4,14-trimethylpregnane class. The absolute configuration of the glucuronate of 3 was assigned by an application of the phenylglycine methyl ester (PGME) method. The new compounds exhibited moderate cytotoxicity against A549 and K562 cell lines, and compound 3 showed antibacterial activity. The cytotoxicity of 1 may be related to the presence of a free phenolic -OH group, as the corresponding O-methoxy derivative 4 is inactive.
Subject(s)
Porifera/chemistry , Saponins/isolation & purification , Sesterterpenes/isolation & purification , Triterpenes/isolation & purification , Animals , Anti-Bacterial Agents/chemistry , Antineoplastic Agents/chemistry , Drug Screening Assays, Antitumor , Humans , K562 Cells , Microbial Sensitivity Tests , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Saponins/chemistry , Saponins/pharmacology , Sesterterpenes/chemistry , Sesterterpenes/pharmacology , Structure-Activity Relationship , Triterpenes/chemistry , Triterpenes/pharmacologyABSTRACT
Gombaspiroketals A-C (1-3), tetracyclic sesterterpenes of a novel skeletal class, were isolated from the Korean marine sponge Clathria gombawuiensis. On the basis of the combined spectroscopic analyses, the structures of these compounds were determined to be highly rearranged sesterterpene spiroketal methoxyacetals (1 and 2) and a corresponding hemiacetal (3). The relative and absolute configurations were assigned by NOESY analysis and ECD calculations, respectively. These compounds exhibited moderate cytotoxicities and antibacterial activities.
Subject(s)
Anti-Bacterial Agents/chemistry , Antineoplastic Agents/chemistry , Furans/chemistry , Porifera/chemistry , Sesquiterpenes/chemistry , Sesterterpenes/chemistry , Spiro Compounds/chemistry , Animals , Anti-Bacterial Agents/isolation & purification , Anti-Bacterial Agents/pharmacology , Antineoplastic Agents/isolation & purification , Antineoplastic Agents/pharmacology , Drug Screening Assays, Antitumor , Marine Biology , Nuclear Magnetic Resonance, Biomolecular , Republic of Korea , Sesquiterpenes/isolation & purification , Sesterterpenes/isolation & purification , Sesterterpenes/pharmacologyABSTRACT
A new peptide, gombamide A (1), was isolated from the marine sponge Clathria gombawuiensis, collected from Korean waters. On the basis of the results of combined spectroscopic analyses, the structure of this compound was determined to be a cyclic C-terminally modified thiohexapeptide containing the unusual amino acid residues para-hydroxystyrylamide (pHSA) and pyroglutamic acid (pyroGlu). The absolute configurations of all amino acid residues were determined to be l by advanced Marfey's analysis. The new compound exhibited weak cytotoxicity against A549 and K562 cell lines as well as moderate inhibitory activity against Na(+)/K(+)-ATPase.
