RESUMEN
A new series of diterpenylquinone/hydroquinones has been prepared by Diels-Alder cycloaddition between three labdanic diterpenoids (myrceocommunic acid, methyl myrceocommunate, and myrceocommunyl acetate) and p-benzoquinone or 1,4-naphthoquinone. Influences of the quinone/hydroquinone fragment and other structural features, such as the different functionalities in the terpenic core, are considered in relation to the cytotoxicity toward neoplastic cells and the selectivity of these diterpenylnaphthoquinones/hydroquinones and anthraquinones. Several compounds showed IC50 values under the micromolar level, and four of these derivatives were evaluated at the NCI screening panel. The results showed an important selectivity toward renal cancer lines, identifying these compounds as a very promising group of antineoplastics.
Asunto(s)
Antineoplásicos/síntesis química , Diterpenos/síntesis química , Quinonas/síntesis química , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Diterpenos/química , Diterpenos/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Ratones , Modelos Moleculares , Quinonas/química , Quinonas/farmacología , Relación Estructura-Actividad , Células Tumorales CultivadasRESUMEN
The bioactive fractions obtained from the extract of Asteriscus vogelii afforded a new humulene derivative, the 8-oxo-6,7,9,10-tetrahydrohumulen-1,12-olide (1), in addition to the known asteriscunolides A (2), C (3) and D (4), and the acids 8-oxo-alpha-humula-6Z,9Z-dien-12-oic acid (5), 8-oxo-alpha-humula-6E,9Z-dien- 12-oic acid (6) and 8-oxo-alpha-humula-6E,9E-dien-12-oic acid (7), characterized as their methyl esters. Evaluation of their phytotoxic and cytotoxic activities was accomplished. Compounds 3 and 4 gave the highest inhibition of plant cell cultures and of the plant Lemna paucicostata. Compound 4 was also the most active against P-338 lymphoma in mice, A-549 carcinoma of human lung, HT-29 carcinoma of human colon and MEL-28 human melanoma.
Asunto(s)
Antineoplásicos Fitogénicos/aislamiento & purificación , Magnoliopsida/química , Sesquiterpenos/aislamiento & purificación , Animales , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Humanos , Ratones , Estructura Molecular , Sesquiterpenos Monocíclicos , Sesquiterpenos/química , Sesquiterpenos/farmacología , Análisis Espectral , Células Tumorales CultivadasRESUMEN
Several aldehydes related to methyl 9-deoxy-9-oxo-alpha-apopicropodophyllate, a selective antitumour agent against the HT-29 colon carcinoma, have been prepared and evaluated for their cytotoxic activities on four neoplastic cell lines (P-388, A-549, HT-29 and MEL-28). All of them lacked the lactone ring but maintained their cytotoxicity at, or under, the microM level.
Asunto(s)
Aldehídos/síntesis química , Aldehídos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Lignanos/química , Animales , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Estructura Molecular , Plasmodium falciparum/efectos de los fármacos , Análisis Espectral , Células Tumorales CultivadasRESUMEN
The effect of selected marine compounds with anti-tumoral activity on the cell microtubule network was tested by immunofluorescence analyses, or by other in vitro analyses involving competition with colchicine or with GTP for tubulin binding and tubulin polymerisation, studies that were carried out in parallel with other microtubule poisons used as controls. Three compounds were found to disorganise the microtubule network: isohomohalichondrin B, LL-15 and ecsteinascidin 743. The first two compounds prevent microtubule assembly and GTP binding to tubulin. Ecteinascidin 743 disorganises the microtubule network but it does not seem to interact directly with tubulin.
Asunto(s)
Antineoplásicos/farmacología , Dioxoles/farmacología , Isoquinolinas/farmacología , Microtúbulos/efectos de los fármacos , Naftalenos/farmacología , Piranos/farmacología , Compuestos de Espiro/farmacología , Citoesqueleto de Actina/efectos de los fármacos , Animales , Células Cultivadas , Guanosina Trifosfato/metabolismo , Células HeLa/efectos de los fármacos , Humanos , Ratones , Tetrahidroisoquinolinas , TrabectedinaRESUMEN
Nineteen cyclolignans of varied structures, most of them isolated from Juniperus sabina leaves, were evaluated for their antineoplastic and antiviral activities. They were subjected to screening against P-388 murine leukemia, A-549 human lung carcinoma, and HT-29 colon carcinoma, while the antiviral assays were performed on herpes simplex virus type 1 infecting fibroblasts of monkey kidney (HSV-1/CV-1) and on vesicular stomatitis virus infecting fibroblasts of hamster kidney (VSV/BHK). A number of substances were active in both types of assays at concentrations below 1 microgram/ml; deoxypodophyllotoxin and beta-peltatin A methyl ether being the most potent compounds in all cases, with IC50 values in the range 2.5-4 ng/ml for the three neoplastic systems.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Antivirales/farmacología , Lignina/farmacología , Animales , Antineoplásicos Fitogénicos/química , Antivirales/química , Línea Celular , Cricetinae , Ensayos de Selección de Medicamentos Antitumorales , Haplorrinos , Humanos , Lignanos , Lignina/química , Ratones , Ratones Endogámicos DBA , Plantas/química , Simplexvirus/efectos de los fármacos , Relación Estructura-Actividad , Células Tumorales Cultivadas , Virus de la Estomatitis Vesicular Indiana/efectos de los fármacosRESUMEN
A series of fused pyrazole derivatives of cyclolignans have been prepared through simple chemical routes and evaluated for their cytotoxic activities in culture cells of P-388 murine leukemia, A-549 lung carcinoma and HT-29 colon carcinoma. Despite the lack of the lactone moiety in their structures, they show IC50 values at microM levels.
Asunto(s)
Antineoplásicos Fitogénicos/síntesis química , Antineoplásicos Fitogénicos/farmacología , Lignanos/síntesis química , Lignanos/farmacología , Pirazoles/síntesis química , Pirazoles/farmacología , Animales , Antineoplásicos Fitogénicos/química , Ensayos de Selección de Medicamentos Antitumorales , Células HT29/efectos de los fármacos , Humanos , Leucemia P388/tratamiento farmacológico , Lignanos/química , Neoplasias Pulmonares/tratamiento farmacológico , Espectroscopía de Resonancia Magnética/métodos , Ratones , Pirazoles/química , Relación Estructura-ActividadRESUMEN
28 cyclolignans, most of them derived from podophyllotoxin, have been evaluated for their antineoplastic and antiviral activities. They were subjected to screening against P-388 murine leukemia, A-549 human lung carcinoma, and HT-29 colon carcinoma, while antiviral assays were performed on herpes simplex virus type I infecting fibroblasts of monkey kidney (HSV/CV-1) and on vesicular stomatitis virus infecting fibroblasts of hamster kidney (VSV/BHK). A number of substances were active in both groups of assays at concentrations below 1 microM; deoxypodophyllotoxin (1) being the most potent compound in all cases.
Asunto(s)
Antineoplásicos Fitogénicos/síntesis química , Antivirales/síntesis química , Podofilotoxina/análogos & derivados , Podofilotoxina/farmacología , Animales , Antineoplásicos Fitogénicos/farmacología , Antivirales/farmacología , Cricetinae , Ensayos de Selección de Medicamentos Antitumorales , Haplorrinos , Humanos , Ratones , Células Tumorales Cultivadas , Virus/efectos de los fármacosRESUMEN
Influences of the quinone/hydroquinone fragment and other structural features are considered in relation with the antineoplastic activity and selectivity of terpenylquinones/hydroquinones. Several compounds have shown IC50 values under the microM level.
Asunto(s)
Antineoplásicos/síntesis química , Hidroquinonas/síntesis química , Quinonas/síntesis química , Terpenos/síntesis química , Animales , Antineoplásicos/farmacología , Muerte Celular/efectos de los fármacos , Humanos , Hidroquinonas/farmacología , Espectroscopía de Resonancia Magnética , Ratones , Quinonas/farmacología , Relación Estructura-Actividad , Terpenos/farmacología , Células Tumorales Cultivadas/efectos de los fármacosRESUMEN
Several prenylhydroquinones have been prepared through Diels-Alder condensation, further functionalized or degraded chemically and then evaluated for their cytotoxic activity against some neoplastic cultured cell lines. A number of them have shown IC50 values under the microM level.
Asunto(s)
Antineoplásicos/síntesis química , Hidroquinonas/síntesis química , Antineoplásicos/química , Antineoplásicos/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Hidroquinonas/química , Hidroquinonas/farmacología , Espectroscopía de Resonancia Magnética , Estructura Molecular , Espectroscopía Infrarroja por Transformada de Fourier , 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
Three cytotoxic triterpenes, sodwanones G [5], H [6], and I [7], have been isolated from a marine sponge. The three structures were determined by interpretation of nmr spectra, and in the case of 5, also on the basis of the X-ray diffraction analysis. The X-ray diffraction analysis of two other earlier reported sodwanones, E [3] and F [4] is also discussed. The cytotoxic activity against several cancer cell lines, has been tested. IC50 values between 20 and 0.02 microM were obtained. Compounds 5 and 6 were 10- and 500-fold, respectively, more cytotoxic to A-549 cells than to any of the other cell lines tested (HT-29, MEL-28, P-388).
Asunto(s)
Antineoplásicos/aislamiento & purificación , Poríferos/química , Triterpenos/aislamiento & purificación , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Espectroscopía de Resonancia Magnética , Ratones , Conformación Molecular , Triterpenos/química , Triterpenos/farmacología , Células Tumorales Cultivadas , Difracción de Rayos XRESUMEN
Nine lignan derivatives (4-12) have been obtained from (-)-yatein by treatment with DDQ and NBS. They showed moderate antineoplastic activity (P-388, A-549, HT-29) compared with podophyllotoxin, but some of them have a better therapeutic index. None of the tested compounds shows anti-viral (HSV-1, VSV) or enzyme inhibitor (ADA, DHFR, GST) activities.