RESUMO
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).
Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Ácidos Graxos/química , Ácidos Graxos/farmacologia , Urocordados/química , Animais , Estrutura Molecular , Staphylococcus aureus/efeitos dos fármacosRESUMO
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).
Assuntos
Aminoácidos/química , Dipeptídeos/farmacologia , Iodobenzenos/farmacologia , Urocordados/metabolismo , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Dipeptídeos/química , Dipeptídeos/isolamento & purificação , Humanos , Iodobenzenos/química , Iodobenzenos/isolamento & purificação , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores , Análise EspectralRESUMO
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.
Assuntos
Amino Álcoois/farmacologia , Urocordados/metabolismo , Amino Álcoois/química , Amino Álcoois/isolamento & purificação , Animais , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Anti-Infecciosos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Humanos , República da Coreia , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores , Análise EspectralRESUMO
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.
Assuntos
Alcaloides/química , Anti-Infecciosos/química , Carbolinas/química , Urocordados/química , Alcaloides/farmacologia , Alcaloides/toxicidade , Aminoaciltransferases/antagonistas & inibidores , Aminoaciltransferases/metabolismo , Animais , Anti-Infecciosos/farmacologia , Anti-Infecciosos/toxicidade , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/metabolismo , Carbolinas/síntese química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cisteína Endopeptidases/metabolismo , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Isocitrato Liase/antagonistas & inibidores , Isocitrato Liase/metabolismo , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores , ATPase Trocadora de Sódio-Potássio/metabolismo , Relação Estrutura-AtividadeRESUMO
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.
Assuntos
4-Butirolactona/análogos & derivados , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Urocordados/química , 4-Butirolactona/química , 4-Butirolactona/isolamento & purificação , 4-Butirolactona/farmacologia , Acetamidas/farmacologia , Animais , Antibacterianos/química , Farmacorresistência Bacteriana/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Linezolida , Biologia Marinha , Testes de Sensibilidade Microbiana , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Oxazolidinonas/farmacologia , República da Coreia , Vancomicina/farmacologiaRESUMO
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.
Assuntos
Furanos/isolamento & purificação , Hidrocarbonetos Bromados/isolamento & purificação , Aminoaciltransferases/antagonistas & inibidores , Animais , Proteínas de Bactérias/antagonistas & inibidores , Cisteína Endopeptidases , Ensaios de Seleção de Medicamentos Antitumorais , Ésteres , Furanos/química , Furanos/farmacologia , Hidrocarbonetos Bromados/química , Hidrocarbonetos Bromados/farmacologia , Isocitrato Liase/antagonistas & inibidores , Testes de Sensibilidade Microbiana , Estrutura Molecular , República da Coreia , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores , Staphylococcus aureus/efeitos dos fármacos , Urocordados/químicaRESUMO
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.