RESUMEN
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.
Asunto(s)
Annonaceae/química , Antiinfecciosos/aislamiento & purificación , Diterpenos/farmacología , Corteza de la Planta/química , Tallos de la Planta/química , Antiinfecciosos/farmacología , Diterpenos/aislamiento & purificación , Indonesia , Medicina Tradicional , Pruebas de Sensibilidad Microbiana , Extractos VegetalesRESUMEN
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.
Asunto(s)
Acetileno/aislamiento & purificación , Annonaceae/química , Antibacterianos/aislamiento & purificación , Ácidos Carboxílicos/aislamiento & purificación , Polímeros/aislamiento & purificación , Acetileno/análogos & derivados , Acetileno/química , Acetileno/farmacología , Alquinos , Antibacterianos/química , Antibacterianos/farmacología , Ácidos Carboxílicos/química , Ácidos Carboxílicos/farmacología , Diinos , Evaluación Preclínica de Medicamentos , Farmacorresistencia Microbiana , Indonesia , Espectroscopía de Resonancia Magnética , Meticilina/farmacología , Estructura Molecular , Mycobacterium smegmatis/efectos de los fármacos , Tallos de la Planta/química , Plantas Medicinales/química , Polímeros/química , Polímeros/farmacología , Poliinos , Espectrofotometría Ultravioleta , Espectroscopía Infrarroja por Transformada de Fourier , Staphylococcus aureus/efectos de los fármacosRESUMEN
Autoxidation of para-aminophenol (PAP) has been proposed to account for the selective nephrotoxicity of this compound. However, other studies suggest that hepatic metabolites of PAP rather than the parent compound may be responsible for renal damage. These studies were designed to investigate PAP metabolism in isolated hepatocytes. We synthesized several proposed metabolites for analysis by HPLC/mass spectrometry and compared those results with HPLC/mass spectrometric analyses of metabolites found after incubating hepatocytes with PAP. Hepatocytes prepared from male Sprague-Dawley rats were incubated in Krebs-Henseleit buffer at 37 degrees C for 5 h with 2.3 mM PAP under an atmosphere of 5% CO2/95% O2. Aliquots were withdrawn at 0.1 h of incubation and then hourly through 5 h of incubation. Reactions were terminated by the addition of acetonitrile. Hepatocyte viability was unaltered with PAP present in the incubation medium. We found that hepatocytes converted PAP to two major metabolites (PAP-GSH conjugates and PAP-N-acetylcysteine conjugates) and several minor metabolites [PAP-O-glucuronide, acetaminophen (APAP), APAP-O-glucuronide, APAP-GSH conjugates, and 4-hydroxyformanilide]. Preincubating hepatoyctes with 1-aminobenzotriazole, an inhibitor of cytochromes P450, did not alter the pattern of PAP metabolism. In conclusion, we found that PAP was metabolized in hepatocytes predominantly to PAP-GSH conjugates and PAP-N-acetylcysteine conjugates in sufficient quantities to account for the nephrotoxicity of PAP.
Asunto(s)
Aminofenoles/metabolismo , Hígado/metabolismo , Acetilcisteína/metabolismo , Aminofenoles/farmacología , Animales , Supervivencia Celular/efectos de los fármacos , Cromatografía Líquida de Alta Presión , Cromatografía de Gases y Espectrometría de Masas , Glutatión/metabolismo , Técnicas In Vitro , Riñón/efectos de los fármacos , Hígado/citología , Hígado/efectos de los fármacos , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
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.
Asunto(s)
Alcaloides/aislamiento & purificación , Mutágenos/aislamiento & purificación , Piperidinas/aislamiento & purificación , Urocordados/química , Alcaloides/farmacología , Animales , Cromatografía en Capa Delgada , Reparación del ADN/efectos de los fármacos , ADN de Hongos/biosíntesis , Espectroscopía de Resonancia Magnética , Pruebas de Mutagenicidad , Mutágenos/farmacología , Piperidinas/farmacología , Levaduras/efectos de los fármacos , Levaduras/genéticaRESUMEN
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.
Asunto(s)
Moléculas de Adhesión Celular/metabolismo , Cnidarios/química , Quinonas/aislamiento & purificación , Receptores Inmunológicos/metabolismo , Animales , Moléculas de Adhesión Celular/efectos de los fármacos , Línea Celular , Humanos , Riñón/efectos de los fármacos , Riñón/metabolismo , Espectroscopía de Resonancia Magnética , Quinonas/farmacología , Receptores Inmunológicos/efectos de los fármacos , Receptores DepuradoresRESUMEN
A new glycopeptide antibiotic complex was isolated from the fermentation culture of Kibdelosporangium aridum subsp. largum (SK&F AAD-609) by affinity chromatography on a D-alanyl-D-alanine agarose column. This major components of the complex were resolved by preparative reversed-phase HPLC. Mild acid hydrolysis showed that the new antibiotics have the same mannosyl aglycon (2) as the aridicins. FAB mass spectrometry, isoelectric focusing, potentiometric titration and carbohydrate and fatty acid analyses were used to determine the structures of the five major components of the complex. These studies showed that the kibdelins differ from the aridicins only in the oxidation level at the C-6 position of the amino sugar. Kibdelin A (5), B (6), C1 (7), C2 (8) and D (9) are a series of N-acylglucosamine analogs containing saturated straight and branched chain C10-C12 fatty acids whereas, in kibdelin D the fatty acid component is (Z)-4-decenoic acid.