Asunto(s)
Antibacterianos/química , Antibacterianos/farmacología , Macrólidos , Streptomyces/metabolismo , Antibacterianos/aislamiento & purificación , Antibacterianos/metabolismo , Candida/efectos de los fármacos , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Natamicina/química , Natamicina/farmacología , Nistatina/farmacologíaRESUMEN
A novel bioactive macrolide, IB-96212 has been isolated from the fermentation broth of a marine actinomycete, L-25-ES25-008. The strain belongs to the genus Micromonospora. The macrolide showed a very strong cytotoxic activity against P-388, and lower but significant activity against A-549, HT-29, and MEL-28 cell lines. We describe the isolation, taxonomy and fermentation of the producing strain as well as the isolation of IB-96212.
Asunto(s)
Antibacterianos/farmacología , Macrólidos , Micromonospora/metabolismo , Antibacterianos/química , Antibacterianos/metabolismo , Antineoplásicos/química , Antineoplásicos/metabolismo , Antineoplásicos/farmacología , Línea Celular , Ensayos de Selección de Medicamentos Antitumorales , Fermentación , Humanos , Pruebas de Sensibilidad Microbiana , Micromonospora/ultraestructura , Microscopía Electrónica de Rastreo , Estructura MolecularRESUMEN
IB-96212, is a new member of spiroketal containing macrolide class of fermentation-derived natural products isolated from mycelial extracts of Micromonospora sp. The structure consists of a new aglycone which possesses a 26-membered macrolide ring system and of one deoxy sugar identified as L-rhodinose, this structure represents the first reported spiroketal macrolide natural product related to other macrolides, such as oligomycins, dunaimycins, citovaricin, rutamycin and ossamycin.
Asunto(s)
Antibacterianos/química , Antineoplásicos/química , Macrólidos , Micromonospora/metabolismo , Estructura Molecular , Espectrometría de Masa Bombardeada por Átomos Veloces , Análisis EspectralRESUMEN
Sesbanimides are cytotoxic compounds, originally isolated in 1983 from seeds of the leguminous plants Sesbania drummondii and Sesbania punicea. In this paper we describe the bacterial production of sesbanimides by two "marine Agrobacterium"; strain PH-103 which produces Sesbanimide-A and strain PH-A034C which produces Sesbanimide-C. The isolation and taxonomy of the producing microorganisms, fermentation and isolation of sesbanimides are reported.
Asunto(s)
Alcaloides , Antineoplásicos Fitogénicos/aislamiento & purificación , Disacáridos/aislamiento & purificación , Piperidinas/aislamiento & purificación , Rhizobium/química , Antineoplásicos Fitogénicos/química , Disacáridos/química , Fermentación , Biología Marina , Piperidinas/química , Rhizobium/clasificación , Rhizobium/metabolismo , Microbiología del AguaRESUMEN
A novel bioactive depsipeptide, thiocoraline, was isolated from the mycelial cake of a marine actinomycete strain L-13-ACM2-092. Based on morphological, cultural, physiological, and chemical characteristics, strain L-13-ACM2-092 was ascribed to the genus Micromonospora. Thiocoraline showed a potent cytotoxic activity against P-388, A-549 and MEL-28 cell lines, and also a strong antimicrobial activity against Gram-positive microorganisms. This compound binds to supercoiled DNA and inhibits RNA synthesis.
Asunto(s)
Antibacterianos/aislamiento & purificación , Antibióticos Antineoplásicos/aislamiento & purificación , Depsipéptidos , Péptidos , Animales , Antibacterianos/farmacología , Antibióticos Antineoplásicos/farmacología , Fermentación , Leucemia P388/tratamiento farmacológico , Pruebas de Sensibilidad Microbiana , Micromonospora , Células Tumorales Cultivadas/efectos de los fármacosRESUMEN
Thiocoraline (1) is a new antitumor antibiotic isolated from the mycelium of Micromonospora sp. L-13-ACM2-092. Its structure was elucidated to be a novel cyclic thiodepsipeptide on the basis of spectroscopic methods.
Asunto(s)
Antibacterianos/química , Antibióticos Antineoplásicos/química , Depsipéptidos , Péptidos , Estructura MolecularAsunto(s)
Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacología , Cumarinas/química , Cumarinas/farmacología , Animales , Antibióticos Antineoplásicos/aislamiento & purificación , Bacillus/química , Bacillus/aislamiento & purificación , Cumarinas/aislamiento & purificación , ADN de Neoplasias/biosíntesis , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Espectroscopía de Resonancia Magnética , Biología Marina , Estructura Molecular , Proteínas de Neoplasias/biosíntesis , Células Tumorales CultivadasRESUMEN
The effects of several members of the family of lamellarins, polyaromatic alkaloids isolated from tunicates belonging to the genus Didemnum, on the growth of several tumour cell lines and on P-glycoprotein (P-gp)-mediated multidrug resistance (MDR), were investigated. Cytotoxicity experiments of lamellarins were performed on a panel of tumour cell lines, including two multidrug-resistant cell lines. Some lamellarins showed good anti-tumour activity, with similar levels of cytotoxicity against both the resistant and their corresponding parental cell lines. Two lamellarins displayed a high potency against lung carcinoma cells. Studies of the resistance modifier activity of the different lamellarins at non-toxic concentrations were also carried out in cells exhibiting MDR, and lamellarin I was selected for the highest chemosensitising activity. At non-toxic doses, verapamil and lamellarin I effectively increased the cytotoxicity of doxorubicin, vinblastine and daunorubicin in a concentration-dependent manner in multidrug-resistant cells, but the potency of lamellarin I as a MDR modulator was 9- to 16-fold higher than that of verapamil. In vitro measurements of rhodamine 123 accumulation in the multidrug-resistant Lo Vo/Dx cells suggest that lamellarin I reverses MDR by directly inhibiting the P-gp-mediated drug efflux. This work underscores the possibility of using these marine-derived compounds as a potential new source of anti-tumoral drugs active on resistant cells as well as of non-toxic modulators of the MDR phenotype.
Asunto(s)
Alcaloides/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Neoplasias del Colon/tratamiento farmacológico , Resistencia a Múltiples Medicamentos/fisiología , Leucemia P388/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/fisiología , Adenocarcinoma/tratamiento farmacológico , Alcaloides/química , Alcaloides/farmacología , Animales , Antimetabolitos Antineoplásicos/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Supervivencia Celular/efectos de los fármacos , Cricetinae , Daunorrubicina/administración & dosificación , Doxorrubicina/administración & dosificación , Resistencia a Antineoplásicos/fisiología , Humanos , Ratones , Rodamina 123 , Rodaminas/metabolismo , Células Tumorales Cultivadas , Verapamilo/administración & dosificación , Vinblastina/administración & dosificaciónRESUMEN
A simple, rapid, sensitive and automatizable method for the detection and quantification of bacterial cell wall inhibitors has been developed. The procedure is characterized by the use of a micro-organism hypersensitive to beta-lactam antibiotics that contains an inducible cytosolic beta-galactosidase; this enzyme is released when the micro-organism cell wall is disrupted by the antibiotic action, and then measured by the use of a chromogenic substrate. The present method allows the detection of beta-lactam traces in other non-beta-lactam antibiotics, and has been successfully applied in the detection of small amounts of beta-lactams in biological fluids such as milk and Actinomycetes fermentation broths. The easy automatization of this method makes it specially suitable for the screening of new antibiotics of natural origin.