RESUMEN
Bioactivity-directed fractionation of an EtOAc extract from the leaves of Miconia lepidota afforded the two benzoquinones 2-methoxy-6-heptyl-1,4-benzoquinone (1) and 2-methoxy-6-pentyl-1,4-benzoquinone (primin) (2). This is the first reported isolation of 1. Both quinones 1 and 2 exhibited activity toward mutant yeast strains based on Saccharomyces cerevisiae, indicative of their cytotoxicity and potential anticancer activity. A number of previously synthesized and new analogues were prepared and tested in the same strains. Compounds 1, 2, 2-methoxy-6-butyl-1,4-benzoquinone (5), and 2-methoxy-6-decyl-1,4-benzoquinone (6) were tested in two cytotoxicity assays. In the M109 tumor cell lines, quinones 1, 2, and 6 had an IC(50) value of 10 microg/mL. In the A2780 cell line, compounds 1, 2 and 5 had IC(50) values of 7.9, 2.9, and 3.2 microg/mL, respectively.
Asunto(s)
Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Benzoquinonas/química , Benzoquinonas/farmacología , Plantas Medicinales/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Benzoquinonas/aislamiento & purificación , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Espectroscopía de Resonancia Magnética , Extractos Vegetales/química , Espectrometría de Masa por Ionización de Electrospray , Relación Estructura-Actividad , Suriname , Células Tumorales Cultivadas , Levaduras/efectos de los fármacosRESUMEN
Bioassay-guided fractionation of the MeOH extract of Swartzia schomburgkii using the engineered yeast strains 1138, 1140, and 1353 as the bioassay tool resulted in the isolation of five active (2, 4-7) and three inactive (1, 3, 8) saponins. Saponins 4 and 6 are previously unreported. The structures of all of the saponins were established based on 1D and 2D NMR spectral analysis, on acid and alkaline hydrolysis followed by TLC and GC-MS, and by comparison with literature data for known compounds. Three of the isolated compounds (4-6) showed weak cytotoxicity against the M-109 cell line.
Asunto(s)
Plantas Medicinales/química , Saponinas/análisis , Antifúngicos/aislamiento & purificación , Antifúngicos/farmacología , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Cromatografía de Gases y Espectrometría de Masas , Hidrólisis , Espectroscopía de Resonancia Magnética , Saponinas/farmacología , Espectrometría de Masa Bombardeada por Átomos Veloces , Suriname , Células Tumorales CultivadasRESUMEN
Bioassay-guided fractionation of the MeOH extract of Eclipta alba using three yeast strains (1138, 1140, and 1353) resulted in the isolation of eight bioactive steroidal alkaloids (1-8), six of which are reported for the first time from nature. The major alkaloid was identified as (20S)(25S)-22,26-imino-cholesta-5,22(N)-dien-3beta-ol (verazine, 3), while the new alkaloids were identified as 20-epi-3-dehydroxy-3-oxo-5,6-dihydro-4,5-dehydroverazine (1), ecliptalbine [(20R)-20-pyridyl-cholesta-5-ene-3beta,23-diol] (4), (20R)-4beta-hydroxyverazine (5), 4beta-hydroxyverazine (6), (20R)-25beta-hydroxyverazine (7), and 25beta-hydroxyverazine (8). Ecliptalbine (4), in which the 22,26-imino ring of verazine was replaced by a 3-hydroxypyridine moiety, had comparable bioactivity to verazine in these assays, while a second alkaloid (8) showed good activity against Candida albicans. All the alkaloids showed weak cytotoxicity against the M-109 cell line.
Asunto(s)
Alcaloides/farmacología , Asteraceae/química , Daño del ADN , ADN/efectos de los fármacos , Fitosteroles/farmacología , Plantas Medicinales/química , Alcaloides/aislamiento & purificación , Candida albicans/efectos de los fármacos , Línea Celular , India , Espectroscopía de Resonancia Magnética , Fitosteroles/aislamiento & purificación , Saccharomyces cerevisiae/efectos de los fármacos , SurinameRESUMEN
A new cytotoxic N-hydroxypyridone, fusaricide (1), was isolated from a Fusarium sp. Its structure was solved by X-ray diffraction and spectroscopic analyses.
Asunto(s)
Antineoplásicos/aislamiento & purificación , Benzopiranos/aislamiento & purificación , Fusarium/química , Piridonas/aislamiento & purificación , Antifúngicos/farmacología , Antineoplásicos/farmacología , Benzopiranos/farmacología , Cristalografía por Rayos X , Hongos/efectos de los fármacos , Regulación Viral de la Expresión Génica/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Piridonas/farmacología , Células Tumorales Cultivadas , Virión/efectos de los fármacosRESUMEN
The new cytotoxic agents rakicidins A and B were isolated from cultured broth of a Micromonospora sp. Spectroscopic and amino acid analysis has shown that rakicidin A is a new cyclic lipopeptide, consisting of 4-amino-penta-2,4-dienoic acid, 3-hydroxy-2,4,16-trimethyl-heptadecanoic acid, sarcosine, and 3-hydroxyasparagine. Rakicidin B differs by one methylene group in the lipid side chain. These compounds exhibited cytotoxicity against the M109 cell line.
Asunto(s)
Antibióticos Antineoplásicos/farmacología , Micromonospora/metabolismo , Animales , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/aislamiento & purificación , Cromatografía Líquida de Alta Presión , Cromatografía en Capa Delgada , Fermentación , Lipopéptidos , Ratones , Estructura Molecular , Péptidos Cíclicos/biosíntesis , Péptidos Cíclicos/química , Péptidos Cíclicos/aislamiento & purificación , Péptidos Cíclicos/farmacología , Análisis Espectral , Células Tumorales CultivadasRESUMEN
A peptide homologous to a region of murine granulocyte-macrophage colony-stimulating factor (mGM-CSF), P27-38, which was shown to be a GM-CSF antagonist, inhibited the function of serotonin release from murine mast cells. Peptide P27-38 inhibited immunoglobulin E (IgE)-mediated serotonin release in a dose-dependent manner when induced by either specific antigen or anti-IgE antibody. In contrast, non-receptor-mediated release of serotonin by agents such as compound 48/80 or the calcium ionophore A23187 were not affected by the GM-CSF antagonist. Similar effects were observed with GM-CSF-neutralizing antibodies. The inhibitory effect of P27-38 and the neutralizing antibodies on serotonin release could be reversed by the addition of exogenous GM-CSF to the stimulated mast cells, indicating that the inhibitory activity was probably due to an effect on endogenously produced GM-CSF. These findings suggest that GM-CSF produced by stimulated mast cells is involved in the regulation of their activity in an autocrine manner.
Asunto(s)
Factor Estimulante de Colonias de Granulocitos y Macrófagos/fisiología , Mastocitos/fisiología , Secuencia de Aminoácidos , Animales , Anticuerpos/farmacología , Masculino , Ratones , Ratones Endogámicos , Datos de Secuencia Molecular , Pruebas de Neutralización , Fragmentos de Péptidos/farmacología , Serotonina/metabolismoRESUMEN
Injection of mice with either natural bovine bone-derived or human recombinant transforming growth factor beta 1 (TGF-beta 1) resulted in a significant increase of the macrophage and macrophage-granulocyte-forming capacity of their macrophage colony-stimulating factor (M-CSF)- and granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent bone marrow precursor cells. The increased potential for generating granulocytes and/or macrophages from bone marrow cells of mice injected with TGF-beta 1 was associated with an increase of the number of M-CSF- and GM-CSF-dependent bone marrow colony-forming units (CFU). The effect was selective, in that in vivo applied TGF-beta 1 did not affect interleukin 3 (IL-3)-dependent CFU. The data suggest that TGF-beta may be useful in recovery of bone marrow granulocyte- and macrophage-forming potentials following depletion caused by chemo- or radiotherapy.
Asunto(s)
Células de la Médula Ósea , Hematopoyesis , Células Madre Hematopoyéticas/citología , Factor de Crecimiento Transformador beta/fisiología , Animales , Factor Estimulante de Colonias de Granulocitos y Macrófagos/farmacología , Granulocitos/citología , Factor Estimulante de Colonias de Macrófagos/farmacología , Macrófagos/citología , RatonesRESUMEN
Madison lung carcinoma (M109), a murine tumor of spontaneous origin, appears to be non-immunogenic, according to 2 commonly employed tests for tumor immunogenicity. However, C.parvum-induced immunopotentiation during the growth of M109 tumor results in post-excision anti-tumor immunity to M109 tumor implants. The C.parvum-potentiated post-excision immunity to M109 is tumor-specific and T-cell-dependent. T cells from mice whose progressive M109 tumors have been excised are capable, on passive transfer, of inhibiting adoptive immunotherapy of T-cell-deficient recipients by spleen cells from mice immunized with an admixture of M109 cells and C.parvum. The data are interpreted as evidence supporting the hypothesis that the apparent lack of anti-tumor immunity in this tumor model is not due to the absence of tumor-associated antigens. We suggest that, instead, in this model the balance between the effector and suppressor arms of the immune response favors tumor-induced immunosuppression, resulting in a magnitude of anti-tumor immunity insufficient for detection by commonly employed tests for tumor immunogenicity. Our study shows that shifting the balance in favor of the effector arm by means of immunopotentiation results in a measurable immune response to an apparently non-immunogenic tumor.