RESUMO
Four diterpenes were isolated from the stem bark of Mitrephora celebica through bioassay-guided fractionation. Ent-trachyloban-19-oic acid (1) and ent-kaur-16-en-19-oic acid (2) were identified as the compounds responsible for the antimicrobial activity of the plant against methicillin-resistant Staphylococcus aureus and Mycobacterium smegmatis. 8(14),15-pimaradien-18-oic acid (3) and 7,15-pimaradien-18-oic acid (4) were isolated from the same fraction and were inactive against the microorganisms.
Assuntos
Annonaceae/química , Anti-Infecciosos/isolamento & purificação , Diterpenos/farmacologia , Casca de Planta/química , Caules de Planta/química , Anti-Infecciosos/farmacologia , Diterpenos/isolamento & purificação , Indonésia , Medicina Tradicional , Testes de Sensibilidade Microbiana , Extratos VegetaisRESUMO
A new polyacetylene carboxylic acid, 13(E),17-octadecadiene-9,11-diynoic acid (13,14-dihydrooropheic acid, 1), and the known 17-octadecene-9,11,13-triynoic acid (oropheic acid, 2) were isolated from the stem bark of Mitrephora celebica through bioassay-guided fractionation. Both compounds demonstrated significant activity against methicillin-resistant Staphylococcus aureus and Mycobacterium smegmatis.
Assuntos
Acetileno/isolamento & purificação , Annonaceae/química , Antibacterianos/isolamento & purificação , Ácidos Carboxílicos/isolamento & purificação , Polímeros/isolamento & purificação , Acetileno/análogos & derivados , Acetileno/química , Acetileno/farmacologia , Alcinos , Antibacterianos/química , Antibacterianos/farmacologia , Ácidos Carboxílicos/química , Ácidos Carboxílicos/farmacologia , Di-Inos , Avaliação Pré-Clínica de Medicamentos , Resistência Microbiana a Medicamentos , Indonésia , Espectroscopia de Ressonância Magnética , Meticilina/farmacologia , Estrutura Molecular , Mycobacterium smegmatis/efeitos dos fármacos , Caules de Planta/química , Plantas Medicinais/química , Polímeros/química , Polímeros/farmacologia , Poli-Inos , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Staphylococcus aureus/efeitos dos fármacosRESUMO
Bioassay-guided fractionation of the MeOH-CH2Cl2 extract of the Micronesian ascidian Pseudodistoma megalarva yielded three new piperidine alkaloids, pseudodistomins D-F (3-5) and the previously reported pseudodistomins B and C (1 and 2). The structure and stereochemistry of these compounds were established by interpretation of spectral data. Pseudodistomins B-F were found to be active in a cell-based assay for DNA damage induction, but the activity was due to an alternative mechanism.
Assuntos
Alcaloides/isolamento & purificação , Mutagênicos/isolamento & purificação , Piperidinas/isolamento & purificação , Urocordados/química , Alcaloides/farmacologia , Animais , Cromatografia em Camada Fina , Reparo do DNA/efeitos dos fármacos , DNA Fúngico/biossíntese , Espectroscopia de Ressonância Magnética , Testes de Mutagenicidade , Mutagênicos/farmacologia , Piperidinas/farmacologia , Leveduras/efeitos dos fármacos , Leveduras/genéticaRESUMO
Bioassay-guided fractionation of the EtOAc extract of the Palauan sponge Axinyssa aplysinoides yielded two novel alkaloids, 1 and 2. The structure of 2-(formylamino)trachyopsane (1) was determined by X-ray analysis; and the structure of N-phenethyl-N'-2-trachyopsanylurea (2), by interpretation of the spectral data.
Assuntos
Antimutagênicos/isolamento & purificação , Sesquiterpenos/isolamento & purificação , Ureia/análogos & derivados , Antimutagênicos/farmacologia , Cristalografia por Raios X , Dano ao DNA , Reparo do DNA/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Sesquiterpenos/farmacologia , Espectrometria de Massas de Bombardeamento Rápido de Átomos , Ureia/isolamento & purificação , Ureia/farmacologiaRESUMO
As part of a search for novel biologically active compounds in the Macrophage Scavenger Receptor (MSR) assay, the EtOAc extract of a gorgonian coral, Pseudopterogorgia rigida, was shown to be active. Bioassay-guided fractionation of the extract yielded curcuphenol, curcuhydroquinone, curcuquinone, and a novel o-quinone, rigidone (1). The structure and stereochemistry of 1 was determined by interpretation of spectral data and chemical transformation.
Assuntos
Moléculas de Adesão Celular/metabolismo , Cnidários/química , Quinonas/isolamento & purificação , Receptores Imunológicos/metabolismo , Animais , Moléculas de Adesão Celular/efeitos dos fármacos , Linhagem Celular , Humanos , Rim/efeitos dos fármacos , Rim/metabolismo , Espectroscopia de Ressonância Magnética , Quinonas/farmacologia , Receptores Imunológicos/efeitos dos fármacos , Receptores DepuradoresRESUMO
As part of a search for novel inhibitors of endothelin converting enzyme (ECE), the MeOH-CH2Cl2 extract of the roots of Dalea filiciformis was shown to be active. Bioassay-guided fractionation of the extract yielded a novel phytoalexin, daleformis (1), whose structure was determined by interpretation of spectral data and X-ray analysis. Daleformis (1) inhibited ECE with an IC50 of 9 microM.
Assuntos
Ácido Aspártico Endopeptidases/antagonistas & inibidores , Benzofuranos/isolamento & purificação , Benzopiranos/isolamento & purificação , Inibidores Enzimáticos/isolamento & purificação , Metaloendopeptidases/antagonistas & inibidores , Raízes de Plantas/química , Plantas Medicinais/química , Acetilação , Benzofuranos/farmacologia , Benzopiranos/farmacologia , Cromatografia em Camada Fina , Cristalografia por Raios X , Enzimas Conversoras de Endotelina , Inibidores Enzimáticos/farmacologia , Conformação Molecular , Espectrofotometria InfravermelhoRESUMO
As part of a search for novel inhibitors of endothelin converting enzyme (ECE), the MeOH extract of a South African sponge, Pachastrella sp., was shown to be active. Bioassay-guided fractionation of the extract yielded a novel sterol sulfate, halistanol disulfate B (1). The structure and stereochemistry of 1 was established mainly by interpretation of spectral data. Disulfate (1) was found to be active at a micromolar concentration in the ECE assay.
Assuntos
Ácido Aspártico Endopeptidases/antagonistas & inibidores , Poríferos/química , Esteróis/isolamento & purificação , Animais , Fenômenos Químicos , Físico-Química , Enzimas Conversoras de Endotelina , Humanos , Espectroscopia de Ressonância Magnética , Metaloendopeptidases , Proteínas Recombinantes/química , Proteínas Recombinantes/farmacologia , Espectrofotometria Infravermelho , Esteróis/farmacologiaRESUMO
As part of a search for novel activators of Ca2+ pumping activity of cardiac SR- (sarcoplasmic reticulum), the EtOAc extract of the Jamaican sponge Plakortis halichondrioides was shown to be active. Bioassay-guided fractionation of the extract followed by preparative TLC and HPLC yielded several known and novel compounds. Three of the novel cyclic peroxides, plakortides F, G, and H (3, 4, and 5) are the subject of this report. Their structures including relative stereochemistry were established by interpretation of spectral data. Micromolar concentrations of plakortides F-H (3-5) were found to significantly enhance Ca2+ uptake by SR.
Assuntos
ATPases Transportadoras de Cálcio/metabolismo , Dioxanos/isolamento & purificação , Miocárdio/enzimologia , Poríferos/metabolismo , Retículo Sarcoplasmático/enzimologia , Animais , Cromatografia Líquida de Alta Pressão , Cromatografia em Camada Fina , Dioxanos/química , Dioxanos/farmacologia , Cães , Ativação Enzimática/efeitos dos fármacos , Coração/efeitos dos fármacos , Técnicas In Vitro , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Espectrofotometria Infravermelho , Espectrofotometria UltravioletaRESUMO
Two novel spirosesquiterpene aldehydes, corallidictyals A [1] and B [2], were isolated as a mixture from the marine sponge Aka (= Siphonodictyon) coralliphagum, and their structures were determined by detailed spectroscopic methods. These compounds were identified in a screen for inhibitors of protein kinase C.
Assuntos
Divisão Celular/efeitos dos fármacos , Poríferos , Proteína Quinase C/antagonistas & inibidores , Sesquiterpenos/isolamento & purificação , Compostos de Espiro/isolamento & purificação , Animais , Chlorocebus aethiops , Humanos , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Modelos Moleculares , Conformação Molecular , Estrutura Molecular , Proteínas Recombinantes/antagonistas & inibidores , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Compostos de Espiro/farmacologia , Relação Estrutura-Atividade , Células VeroRESUMO
As part of a search for novel inhibitors of HIV-1 reverse transcriptase, the acetone extract of the giant African snail, Achatina fulica, was shown to be active. Fractionation of the extract yielded inophyllums A, B, C, and E and calophyllolide (1a, 2a, 3a, 3b, and 6), previously isolated from Calophyllum inophyllum Linn., a known source of nutrition for A. fulica. From a methanol/methylene chloride extract of C. inophyllum, the same natural products in considerably greater yield were isolated in addition to a novel enantiomer of soulattrolide (4), inophyllum P (2b), and two other novel compounds, inophyllums G-1 (7) and G-2 (8). The absolute stereochemistry of inophyllum A (1a) was determined to be 10(R), 11(S), 12(S) from a single-crystal X-ray analysis of its 4-bromobenzoate derivative, and the relative stereochemistries of the other inophyllums isolated from C. inophyllum were established by a comparison of their 1H NMR NOE values and coupling constants to those of inophyllum A (1a). Inophyllums B and P (2a and 2b) inhibited HIV reverse transcriptase with IC50 values of 38 and 130 nM, respectively, and both were active against HIV-1 in cell culture (IC50 of 1.4 and 1.6 microM). Closely related inophyllums A, C, D, and E, including calophyllic acids, were significantly less active or totally inactive, indicating certain structural requirements in the chromanol ring. Altogether, 11 compounds of the inophyllum class were isolated from C. inophyllum and are described together with the SAR of these novel anti-HIV compounds.
Assuntos
Cromanos/isolamento & purificação , HIV-1 , Inibidores da Transcriptase Reversa , Árvores , Acetilação , Animais , Cromanos/química , Cromanos/farmacologia , Cristalização , Cristalografia por Raios X , Transcriptase Reversa do HIV , HIV-1/efeitos dos fármacos , HIV-1/fisiologia , Espectroscopia de Ressonância Magnética , Conformação Molecular , Estrutura Molecular , Caramujos/química , Relação Estrutura-AtividadeRESUMO
Three new imidazole alkaloids, leucettamines A [1] and B [2] and leucettamidine [3], have been isolated from the Palauan sponge Leucetta microraphis. Their structures were established on the basis of extensive spectral analyses. Leucettamine A showed potent leukotriene B4 receptor binding activity (K(i) = 1.3 microM), while leucettamine B was essentially inactive (K(i) = 100 microM) and leucettamidine showed significant activity (K(i) = 5.3 microM). With leucettamine A identified as a pure LTB4 receptor antagonist, a new structure lead is presented to inflammation therapy.
Assuntos
Alcaloides/farmacologia , Dioxóis/isolamento & purificação , Imidazóis/isolamento & purificação , Imidazóis/farmacologia , Poríferos/química , Receptores Imunológicos/antagonistas & inibidores , Animais , Células Cultivadas , Dioxóis/farmacologia , Cromatografia Gasosa-Espectrometria de Massas , Espectroscopia de Ressonância Magnética , Receptores Imunológicos/metabolismo , Receptores do Leucotrieno B4 , Espectrometria de Massas de Bombardeamento Rápido de Átomos , Relação Estrutura-AtividadeRESUMO
The fungus Syncephalastrum racemosum (Cohn) Schroeter was found to transform the fungicide metalaxyl [N-(2,6-dimethylphenyl)-N-(methoxyacetyl)-alanine methyl ester] in pure culture. After 21 days of incubation in a basal medium amended with 5 mug of metalaxyl per ml, more than 80% of the compound was transformed by the fungus. The transformation rates decreased as the concentrations of metalaxyl increased from 5 to 100 mug/ml. No transformation was observed when the concentration of metalaxyl was higher than 200 mug/ml. Two isomeric metabolites and a mixture of two other isomeric metabolites were isolated from the organic extract of the growth medium and identified as N-(2-methyl-6-hydroxymethylphenyl)-N- and N-(2-hydroxymethyl-6-methylphenyl)-N-(methoxyacetyl)-alanine methyl ester and N-(3-hydroxy- and N-(5-hydroxy-2,6-dimethyl-phenyl)-N-(methoxyacetyl)-alanine methyl ester according to their mass-spectral and nuclear magnetic resonance-spectral characteristics. Benzylic hydroxylation of the methyl side chains and/or aromatic hydroxylation appeared to be the major reactions involved in the metabolism of metalaxyl.