RESUMO
Psammocindoles A-C (1-3), a new class of indole alkaloids, were isolated from a Psammocinia vermis sponge. By combined spectroscopic analyses, the structures of these compounds were determined to be the indole-γ-lactams derived from three amino acid residues. In addition, an enantiomer psammocindole D (4), and the N-lactam isomers isopsammocindoles A-D (5-8) were also synthesized. These natural products and synthetic analogues were found to significantly stimulate adiponectin secretion in human bone marrow mesenchymal stem cells.
Assuntos
Alcaloides Indólicos/química , Lactamas/química , Células-Tronco Mesenquimais/efeitos dos fármacos , Poríferos/química , Animais , Produtos Biológicos , Humanos , Alcaloides Indólicos/isolamento & purificação , Lactamas/isolamento & purificação , Células-Tronco Mesenquimais/química , Estrutura Molecular , EstereoisomerismoRESUMO
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.
Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Antineoplásicos/farmacologia , Alcaloides Indólicos/farmacologia , Poríferos/metabolismo , Células A549 , Aminoaciltransferases/antagonistas & inibidores , Aminoaciltransferases/metabolismo , Animais , Antibacterianos/isolamento & purificação , Antifúngicos/isolamento & purificação , Antineoplásicos/isolamento & purificação , Bactérias/efeitos dos fármacos , Bactérias/enzimologia , Bactérias/crescimento & desenvolvimento , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Cisteína Endopeptidases/metabolismo , Fungos/efeitos dos fármacos , Fungos/crescimento & desenvolvimento , Humanos , Alcaloides Indólicos/isolamento & purificação , Células K562 , Testes de Sensibilidade Microbiana , Estrutura Molecular , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Relação Estrutura-AtividadeRESUMO
Twelve new sesterterpenes along with eight known sesterterpenes were isolated from the marine sponge Hyrtios erectus collected off the coast of Chuuk Island, the Federated State of Micronesia. Based upon a combination of spectroscopic and computational analyses, these compounds were determined to be eight glycine-bearing scalaranes (1-8), a 3-keto scalarane (9), two oxidized-furan-bearing scalaranes (10 and 11), and a salmahyrtisane (12). Several of these compounds exhibited weak antiproliferation against diverse cancer cell lines as well as moderate anti-angiogenesis activities. The antiproliferative activity of new compound 4 was found to be associated with G0/G1 arrest in the cell cycle.
Assuntos
Antineoplásicos/farmacologia , Células Hep G2/efeitos dos fármacos , Poríferos/química , Sesterterpenos/farmacologia , Animais , Antineoplásicos/química , Ciclo Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Micronésia , Oceanos e Mares , Sesterterpenos/químicaRESUMO
Two new sceptrin derivatives (1,2) and eight structurally-related known bromopyrrole-bearing alkaloids were isolated from the tropical sponge Agelas kosrae. By a combination of spectroscopic methods, the new compounds, designated dioxysceptrin (1) and ageleste C (2), were determined to be structural analogs of each other that differ at the imidazole moiety. Dioxysceptrin was also found to exist as a mixture of α-amido epimers. The sceptrin alkaloids exhibited weak cytotoxicity against cancer cells. Compounds 1 and 2 also moderately exhibited anti-angiogenic and isocitrate lyase-inhibitory activities, respectively.
Assuntos
Agelas/química , Alcaloides/farmacologia , Produtos Biológicos/farmacologia , Pirróis/farmacologia , Alcaloides/química , Alcaloides/isolamento & purificação , Inibidores da Angiogênese/química , Inibidores da Angiogênese/isolamento & purificação , Inibidores da Angiogênese/farmacologia , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Produtos Biológicos/isolamento & purificação , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Ensaios Enzimáticos , Células Endoteliais da Veia Umbilical Humana , Humanos , Isocitrato Liase/antagonistas & inibidores , Pirróis/química , Pirróis/isolamento & purificação , EstereoisomerismoRESUMO
Three new cyclopeptides, phakellistatins 20-22 (1-3), as well as 10 known cyclopeptides of the same structural class were isolated from the tropical sponge Stylissa flabelliformis. By a combination of chemical and spectroscopic methods, the structures of the new compounds were determined to be an epimeric mixture of cycloheptapeptides (1) and two epimeric cyclodecapeptides (2 and 3) related to the phakellistatins. The cyclopeptides were evaluated for in vitro cytotoxicity against a variety of cancer cell lines, and compounds 2 and 3 exhibited significant activity.
Assuntos
Peptídeos Cíclicos/química , Poríferos/química , Células A549 , Animais , Linhagem Celular Tumoral , Células HCT116 , Humanos , Células K562 , Peptídeos Cíclicos/farmacologiaRESUMO
Five new manzamine alkaloids (1-5) and new salt forms of two known manzamines (6 and 7), along with seven known compounds (8-14) of the same structural class, were isolated from an Indonesian Acanthostrongylophora sp. sponge. On the basis of the results of combined spectroscopic analyses, the structure of kepulauamine A (1) was determined to possess an unprecedented pyrrolizine moiety, while others were functional group variants of known manzamines. These compounds exhibited weak cytotoxicity, moderate antibacterial activity, and mild inhibition against the enzyme isocitrate lyase.
Assuntos
Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Carbazóis/isolamento & purificação , Carbazóis/farmacologia , Isocitrato Liase/efeitos dos fármacos , Pirrolnitrina/isolamento & purificação , Pirrolnitrina/farmacologia , Alcaloides/química , Animais , Antibacterianos/química , Carbazóis/química , Indonésia , Isocitrato Liase/química , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Poríferos , Pirrolnitrina/químicaRESUMO
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.
Assuntos
Antineoplásicos/isolamento & purificação , Callyspongia/química , Compostos Macrocíclicos/isolamento & purificação , Nitrogênio/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Células K562 , Compostos Macrocíclicos/química , Compostos Macrocíclicos/farmacologia , Micronésia , Conformação Molecular , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Oceanos e MaresRESUMO
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.
Assuntos
Citotoxinas/isolamento & purificação , Dysidea/química , Sesquiterpenos/isolamento & purificação , Terpenos/isolamento & purificação , Animais , Citotoxinas/química , Citotoxinas/farmacologia , Humanos , Células K562 , Micronésia , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Sesquiterpenos/química , Sesquiterpenos/farmacologia , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores , Terpenos/químicaRESUMO
Two new peptides, chujamides A (1) and B (2), were isolated from the marine sponge Suberites waedoensis, which was collected from Korean waters. Based upon the results of the combined spectroscopic analyses, the structures of these compounds were determined to be proline-riched and cyclic cystine bridged dodeca- and undecapeptides. The absolute configurations of all amino acid residues were determined to be l by advanced Marfey's analysis. The new compounds exhibited weak cytotoxicities against A549 and K562 cell-lines, and compound 2 also demonstrated moderate inhibitory activity against Naâº/Kâº-ATPase.
Assuntos
Hidrocarbonetos Aromáticos com Pontes/química , Cisteína/química , Peptídeos Cíclicos/química , Poríferos/química , Aminoácidos/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Hidrocarbonetos Aromáticos com Pontes/isolamento & purificação , Linhagem Celular Tumoral , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Humanos , Peptídeos Cíclicos/isolamento & purificação , Peptídeos Cíclicos/farmacologia , Prolina/química , República da Coreia , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidoresRESUMO
The suvanines, a new suvanine salt, five new (2, 4-8) and two known sesterterpenes from the same structural class, and two new modified lipids (9 and 10) were isolated from a Coscinoderma sp. sponge collected from Chuuk Island, Micronesia. On the basis of the results of combined spectroscopic and chemical analyses, a new suvanine salt was determined to be the suvanine N,N-dimethyl-1,3-dimethylherbipoline salt (2) and suvanine-lactam derivatives (4-8) formed by condensations between an oxidized furan moiety and amino acids. The lipid metabolites were found to be new derivatives of the taurine-containing deacyl irciniasulfonic acid class. The suvanines exhibited moderate cytotoxicities against the K562 and A549 cell lines, while the new suvanine salt (2) had significant antibacterial activity.
Assuntos
Antibacterianos/isolamento & purificação , Antineoplásicos/isolamento & purificação , Poríferos/química , Sesterterpenos/isolamento & purificação , Ácidos Sulfônicos/isolamento & purificação , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Células K562 , Testes de Sensibilidade Microbiana , Micronésia , Ressonância Magnética Nuclear Biomolecular , Sesterterpenos/química , Sesterterpenos/farmacologia , Ácidos Sulfônicos/química , Ácidos Sulfônicos/farmacologiaRESUMO
Four new cytotoxic diterpenoid pseudodimers (2-5), along with a previously reported one, gukulenin A (1), were isolated from the marine sponge Phorbas gukhulensis collected off the coast of Gagu-do, Korea. These novel compounds, designated gukulenins C-F (2-5), were determined by extensive spectroscopic analyses to be pseudodimers of the gagunins, like gukulenin A. The termini of the tropolone-containing side chains in gukulenins C-E (2-4) were found to have diverse modifications involving acetamides or taurine, whereas gukulenin F (5) was formed from 1 by the ring-opening of a cyclic hemiketal. The relative and absolute configurations were assigned by Murata's and modified Snatzke's methods using a HETLOC experiment and a CD measurement of a dimolybdenum complex, respectively. All of these compounds exhibited significant cytotoxicity against the K562 and A549 cell lines.
Assuntos
Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Poríferos/química , Animais , Antineoplásicos/química , Diterpenos/química , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Células K562 , Biologia Marinha , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , República da Coreia , Taurina/química , Terpenos/química , Terpenos/farmacologiaRESUMO
Seventeen bromotyrosine-derived metabolites, including eight new compounds, were isolated from a Micronesian sponge of the genus Suberea. Four of the new compounds were psammaplysin derivatives (10-13), and the other four were ceratinamine derivatives (14-17). Of the compounds obtained, the psammaplysins exhibited cytotoxicity against human cancer cell lines (GI50 values down to 0.8 µM), while the ceratinamine and moloka'iamine analogues showed almost no activity. These results suggest that the spirooxepinisoxazoline ring system is a requirement for cytotoxicity and, therefore, may serve as an attractive molecular scaffold for the development of a potent anticancer agent.
Assuntos
Antineoplásicos/farmacologia , Bromobenzenos/isolamento & purificação , Bromobenzenos/farmacologia , Formamidas/isolamento & purificação , Formamidas/farmacologia , Nitrilas/isolamento & purificação , Nitrilas/farmacologia , Poríferos/química , Compostos de Espiro/isolamento & purificação , Compostos de Espiro/farmacologia , Tirosina/análogos & derivados , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Bromobenzenos/química , Ensaios de Seleção de Medicamentos Antitumorais , Formamidas/química , Humanos , Biologia Marinha , Estrutura Molecular , Nitrilas/química , Ressonância Magnética Nuclear Biomolecular , Compostos de Espiro/química , Tirosina/química , Tirosina/isolamento & purificação , Tirosina/farmacologiaRESUMO
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.
Assuntos
Antineoplásicos/isolamento & purificação , Peptídeos Cíclicos/isolamento & purificação , Poríferos/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Biologia Marinha , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Peptídeos Cíclicos/química , Peptídeos Cíclicos/farmacologia , República da Coreia , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidoresRESUMO
Densanins A (1) and B (2) were isolated from the sponge Haliclona densaspicula. On the basis of spectral data and the Mosher ester method, the complete structures were characterized as hexacyclic diamine alkaloids, which were probably derived from 3-alkylpyridine. Compounds 1 and 2 showed relatively potent inhibitory effects on lipopolysaccharide-induced nitric oxide production in BV2 microglial cells with IC(50) values of 1.05 and 2.14 µM, respectively.
Assuntos
Alcaloides/isolamento & purificação , Diaminas/isolamento & purificação , Haliclona/química , Pirróis/isolamento & purificação , Alcaloides/química , Alcaloides/farmacologia , Animais , Diaminas/química , Diaminas/farmacologia , Lipopolissacarídeos/farmacologia , Biologia Marinha , Camundongos , Microglia/efeitos dos fármacos , Estrutura Molecular , Óxido Nítrico/biossíntese , Pirróis/química , Pirróis/farmacologia , República da CoreiaRESUMO
Eight novel cyclic bis-1,3-dialkylpyridiniums, as well as two known compounds from the cyclostellettamine class, were isolated from the sponge Haliclona sp. from Korea. Structures of these novel compounds were determined using combined NMR and FAB-MS/MS analyses. Several of these compounds exhibited moderate cytotoxic and antibacterial activities against A549 cell-line and Gram-positive strains, respectively. The structure-activity relationships of cyclostellettamines are discussed based on their bioactivities.
Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Haliclona/química , Poríferos/química , Animais , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Coreia (Geográfico) , Espectroscopia de Ressonância Magnética/métodos , Espectrometria de Massas/métodos , Relação Estrutura-AtividadeRESUMO
Five new nortriterpene glycosides, along with eight known compounds of the sarasinoside class, were isolated from the tropical sponge Lipastrotethya sp. collected from Chuuk, Micronesia. The structures of these new compounds, designated as sarasinosides N-R (9-13), were determined by combined spectroscopic and chemical methods. The aglycone portions of 10-13 were found to be unprecedented among nortriterpeneoids on the basis of extensive NMR analyses. Several of these compounds exhibited cytotoxicity against A549 and K562 cell lines as well as weak inhibitory activity against Na(+)/K(+)-ATPase.
Assuntos
Antineoplásicos/isolamento & purificação , Glicosídeos/isolamento & purificação , Triterpenos/isolamento & purificação , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Glicosídeos/química , Glicosídeos/farmacologia , Humanos , Células K562 , Micronésia , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Poríferos/química , Triterpenos/química , Triterpenos/farmacologiaRESUMO
Three sphingosine 4-sulfates (1-3) and a lysophosphatidylglycerol (4) were isolated from the Korean sponge Spirastrella abata. The structures of these compounds were determined based on the combined results of spectroscopic analyses. Based on the results of combined synthesis and comparison of specific rotation and circular dichroism, the absolute configurations of 1-3 were found to be enantiomeric to the previously isolated metabolites. The configurations of 4 were also partially determined by similar chemical and spectroscopic methods. The compounds exhibited significant cytotoxicity and weak antimicrobial activity (1), as well as weak-to-moderate inhibitory activity against isocitrate lyase and Na(+)/K(+)-ATPase. A structure-activity relationship was found for the sphingosine 4-sulfates.
Assuntos
Lisofosfolipídeos/isolamento & purificação , Poríferos/química , Esfingosina/isolamento & purificação , Sulfatos/isolamento & purificação , Animais , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Antifúngicos/química , Antifúngicos/isolamento & purificação , Antifúngicos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Bactérias/efeitos dos fármacos , Disponibilidade Biológica , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/farmacologia , Fungos/efeitos dos fármacos , Humanos , Isocitrato Liase/antagonistas & inibidores , Isocitrato Liase/metabolismo , Células K562 , Lisofosfolipídeos/química , Lisofosfolipídeos/farmacologia , Testes de Sensibilidade Microbiana , Conformação Molecular , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores , ATPase Trocadora de Sódio-Potássio/metabolismo , Esfingosina/análogos & derivados , Esfingosina/farmacologia , Relação Estrutura-Atividade , Sulfatos/química , Sulfatos/farmacologiaRESUMO
Nine new triterpene galactosides and aglycones, along with three known compounds from the rare pouoside class, were isolated from the tropical sponge Lipastrotethya sp. collected from Micronesia. The structures of these new compounds were determined by combined spectroscopic methods and designated as pouosides F-I (4, 8, 10, and 12) and pouogenins A-E (5-7, 9, and 11). The absolute configurations of the asymmetric centers and the cyclohexenone moiety, which had been previously undetermined, were assigned by NOESY analyses and Mosher's methods. Several of these compounds exhibited weak cytotoxicity against the K562 cell line.
Assuntos
Antineoplásicos/isolamento & purificação , Galactosídeos/isolamento & purificação , Poríferos/química , Triterpenos/isolamento & purificação , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Galactosídeos/química , Galactosídeos/farmacologia , Humanos , Células K562 , Micronésia , Estrutura Molecular , Triterpenos/química , Triterpenos/farmacologiaRESUMO
Eight new sesterterpenes (2, 5, and 10-15), including structurally related pentaprenyl hydroquinones (2 and 5), and seven known ones of the same structural classes were isolated from the sponge Coscinoderma sp., collected from Chuuk Island, Micronesia. On the basis of the results of combined spectroscopic analyses, the new compounds were determined to be derivatives of the halisulfates and suvanine. These compounds exhibited moderate cytotoxicity against the K562 cell line and inhibitory activities against isocitrate lyase, sortase A, and Na+/K+-ATPase; significant structure-activity relationships were evident.
Assuntos
Antineoplásicos/isolamento & purificação , Poríferos/química , Sesterterpenos/isolamento & purificação , Aminoaciltransferases/antagonistas & inibidores , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Proteínas de Bactérias/antagonistas & inibidores , Cisteína Endopeptidases , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Isocitrato Liase/antagonistas & inibidores , Células K562 , Micronésia , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Sesterterpenos/química , Sesterterpenos/farmacologia , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores , Relação Estrutura-AtividadeRESUMO
Two new pyrroloiminoquinone alkaloids of the discorhabdin class, along with 12 compounds including one previously described synthetic derivative of the same and related skeletal classes, were isolated from the sponge Sceptrella sp., collected from Gageodo, Korea. The structures of these new compounds, designated as (-)-3-dihydrodiscorhabdin D (11) and (-)-discorhabdin Z (12), were determined by combined spectroscopic analyses. Compound 12 possesses an unusual hemiaminal group among the discorhabdin alkaloids. These compounds exhibited moderate to significant cytotoxicity, antibacterial activity, and inhibitory activity against sortase A.