ABSTRACT
Five new bicyclic carboxylic acids were obtained by antibacterial activity-guided isolation from a Korean colonial tunicate Didemnum sp. Their structures were elucidated by the interpretation of NMR, MS and CD spectroscopic data. They all belong to the class of aplidic acids. Three of them were amide derivatives (1-3), and the other two were dicarboxylic derivatives (4 and 5). The absolute configurations were determined by a bisignate pattern of CD spectroscopy, which revealed that the absolute configurations of amides were opposite to those of dicarboxylates at every stereogenic centers. Compound 2 exhibited the most potent antibacterial activity (MIC, 2 µg/mL).
Subject(s)
Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Fatty Acids/chemistry , Fatty Acids/pharmacology , Urochordata/chemistry , Animals , Molecular Structure , Staphylococcus aureus/drug effectsABSTRACT
Four new iodobenzene-containing dipeptides (1-4), a related bromotryptophan-containing dipeptide (5), and an iodophenethylamine (6) were isolated from the ascidian Aplidium sp. collected off the coast of Chuja-do, Korea. The structures of these novel compounds, designated as apliamides A-E (1-5) and apliamine A (6) were determined via combined spectroscopic analyses. The absolute configuration of the amino acid residue in 1 was determined by advanced Marfey's analysis. Several of these compounds exhibited moderate cytotoxicity and significant inhibition against Na+/K+-ATPase (4).
Subject(s)
Amino Acids/chemistry , Dipeptides/pharmacology , Iodobenzenes/pharmacology , Urochordata/metabolism , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/isolation & purification , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Dipeptides/chemistry , Dipeptides/isolation & purification , Humans , Iodobenzenes/chemistry , Iodobenzenes/isolation & purification , Sodium-Potassium-Exchanging ATPase/antagonists & inhibitors , Spectrum AnalysisABSTRACT
Seven new amino alcohol compounds, pseudoaminols A-G (1-7), were isolated from the ascidian Pseudodistoma sp. collected off the coast of Chuja-do, Korea. Structures of these new compounds were determined by analysis of the spectroscopic data and from chemical conversion. The presence of an N-carboxymethyl group in two of the new compounds (6 and 7) is unprecedented among amino alcohols. Several of these compounds exhibited moderate antimicrobial activity and cytotoxicity, as well as weak inhibitory activity toward Na+/K+-ATPase.
Subject(s)
Amino Alcohols/pharmacology , Urochordata/metabolism , Amino Alcohols/chemistry , Amino Alcohols/isolation & purification , Animals , Anti-Infective Agents/chemistry , Anti-Infective Agents/isolation & purification , Anti-Infective Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/isolation & purification , Antineoplastic Agents/pharmacology , Humans , Republic of Korea , Sodium-Potassium-Exchanging ATPase/antagonists & inhibitors , Spectrum AnalysisABSTRACT
Six new (1, 2, and 5-8) and three known (3, 4, and 9) butenolide metabolites were isolated from the tunicate Pseudodistoma antinboja by activity-guided fractionations. The structures were elucidated by combined NMR and MS spectroscopic methods. These compounds were evaluated for their antibacterial activity, and most of them exhibited moderate to significant activity that selectively targeted Gram-positive strains and did not exhibit cytotoxicity in the MTT assay at 100 µM. Cadiolides 5-9 in particular exhibited significant antibacterial activity that was comparable to or even better than those of marketed drugs such as vancomycin and linezolid against all of the drug-resistant strains tested.
Subject(s)
4-Butyrolactone/analogs & derivatives , Anti-Bacterial Agents/isolation & purification , Anti-Bacterial Agents/pharmacology , Urochordata/chemistry , 4-Butyrolactone/chemistry , 4-Butyrolactone/isolation & purification , 4-Butyrolactone/pharmacology , Acetamides/pharmacology , Animals , Anti-Bacterial Agents/chemistry , Drug Resistance, Bacterial/drug effects , Gram-Positive Bacteria/drug effects , Linezolid , Marine Biology , Microbial Sensitivity Tests , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Oxazolidinones/pharmacology , Republic of Korea , Vancomycin/pharmacologyABSTRACT
Nine new compounds, tris-aromatic furanones (1, 2, 3a, 3b, and 4) and related bis-aromatic diesters (5a, 5b, 6a, and 6b), are described from the ascidian Synoicum sp. collected off the coast of Chuja-do, Korea. The structures of these compounds, designated as cadiolides E and G-I (1-4) and synoilides A and B (5 and 6), were determined by extensive spectroscopic analyses. The absolute configuration at the asymmetric center of cadiolide G (2) was assigned by ECD analysis. Of these new compounds, cadiolide I and the synoilides possess unprecedented carbon skeletons. Several of these compounds exhibited significant inhibition against diverse bacterial strains as well as moderate inhibition against the enzymes sortase A, isocitrate lyase, and Na(+)/K(+)-ATPase.
Subject(s)
Furans/isolation & purification , Hydrocarbons, Brominated/isolation & purification , Aminoacyltransferases/antagonists & inhibitors , Animals , Bacterial Proteins/antagonists & inhibitors , Cysteine Endopeptidases , Drug Screening Assays, Antitumor , Esters , Furans/chemistry , Furans/pharmacology , Hydrocarbons, Brominated/chemistry , Hydrocarbons, Brominated/pharmacology , Isocitrate Lyase/antagonists & inhibitors , Microbial Sensitivity Tests , Molecular Structure , Republic of Korea , Sodium-Potassium-Exchanging ATPase/antagonists & inhibitors , Staphylococcus aureus/drug effects , Urochordata/chemistryABSTRACT
Six ß-carboline alkaloids (1-6) of the eudistomin Y class were isolated from the Korean ascidian Synoicum sp. These compounds were chemically converted to a known compound, eudistomin Y(1) (7) and six new derivatives, designated eudistomins Y(8)-Y(13) (8-13). Several of these natural and synthetic compounds exhibited moderate to significant antimicrobial activity, weak cytotoxic activity, and inhibitory activities toward sortase A, isocitrate lyase, and Na(+)/K(+)-ATPase. Structure-activity relationships were also deduced.
Subject(s)
Alkaloids/chemistry , Anti-Infective Agents/chemistry , Carbolines/chemistry , Urochordata/chemistry , Alkaloids/pharmacology , Alkaloids/toxicity , Aminoacyltransferases/antagonists & inhibitors , Aminoacyltransferases/metabolism , Animals , Anti-Infective Agents/pharmacology , Anti-Infective Agents/toxicity , Bacterial Proteins/antagonists & inhibitors , Bacterial Proteins/metabolism , Carbolines/chemical synthesis , Cell Line, Tumor , Cell Survival/drug effects , Cysteine Endopeptidases/metabolism , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Humans , Isocitrate Lyase/antagonists & inhibitors , Isocitrate Lyase/metabolism , Sodium-Potassium-Exchanging ATPase/antagonists & inhibitors , Sodium-Potassium-Exchanging ATPase/metabolism , Structure-Activity RelationshipABSTRACT
One isoprenoid, tuberatolide A (1), meroterpenoids tuberatolide B (2) and 2'-epi-tuberatolide B (3), and the known meroterpenoids yezoquinolide (4), (R)-sargachromenol (5), and (S)-sargachromenol (6) were isolated from the Korean marine tunicate Botryllus tuberatus. The structures of these compounds were elucidated by NMR, MS, and CD spectroscopic analyses. These terpenoids antagonized the chenodeoxycholic acid (CDCA)-activated human farnesoid X receptor (hFXR) in a cell-based co-transfection assay with IC(50) values as low as 1.5 µM without significant effect on steroid receptors. Furthermore, they released the co-activator peptide from the CDCA-bound hFXR ligand binding domain in cell-free surface plasmon resonance experiments.
