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1.
Eur Cell Mater ; 41: 31-39, 2021 01 05.
Artículo en Inglés | MEDLINE | ID: mdl-33400815

RESUMEN

Bioactive glasses (BAG) are used as bone-graft substitutes in orthopaedic surgery. A specific BAG scaffold was developed by sintering BAG-S53P4 granules. It is hypothesised that this scaffold can be used as a bone substitute to fill bone defects and induce a bioactive membrane (IM) around the defect site. Beyond providing the scaffold increased mechanical strength, that the initial inflammatory reaction and subsequent IM formation can be enhanced by coating the scaffolds with poly(DL-lactide-co-glycolide) (PLGA) is also hypothesised. To study the immunomodulatory effects, BAG-S53P4 (± PLGA) scaffolds were placed on monolayers of primary human macrophage cultures and the production of various pro- and anti-inflammatory cytokines was assessed using reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) and ELISA. To study the osteogenic effects, BAG-S53P4 (± PLGA) scaffolds were cultured with rabbit mesenchymal stem cells and osteogenic differentiation was evaluated by RT-qPCR and matrix mineralisation assays. The scaffold ion release was quantified and the BAG surface reactivity visualised. Furthermore, the pH of culture media was measured. BAG-S53P4 scaffolds had both anti-inflammatory and osteogenic properties that were likely attributable to alkalinisation of the media and ion release from the scaffold. pH change, ion release, and immunomodulatory properties of the scaffold could be modulated by the PLGA coating. Contrary to the hypothesis, the coating functioned by attenuating the BAG surface reactions and subsequent anti-inflammatory properties, rather than inducing an elevated inflammatory response compared to BAG-S53P4 alone. These results further validated the use of BAG-S53P4 (± PLGA) scaffolds as bone substitutes and indicate that scaffold properties can be tailored to a specific clinical need.


Asunto(s)
Sustitutos de Huesos , Células Madre Mesenquimatosas , Osteonecrosis , Animales , Tratamiento Basado en Trasplante de Células y Tejidos , Osteogénesis , Conejos , Andamios del Tejido
3.
Adv Exp Med Biol ; 875: 529-38, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26611001

RESUMEN

Like elephants, baleen whales produce low-frequency (LF) and even infrasonic (IF) signals, suggesting they may be particularly susceptible to underwater anthropogenic sound impacts. Analyses of computerized tomography scans and histologies of the ears in five baleen whale and two elephant species revealed that LF thresholds correlate with basilar membrane thickness/width and cochlear radii ratios. These factors are consistent with high-mass, low-stiffness membranes and broad spiral curvatures, suggesting that Mysticeti and Proboscidea evolved common inner ear adaptations over similar time scales for processing IF/LF sounds despite operating in different media.


Asunto(s)
Organismos Acuáticos/fisiología , Oído/fisiología , Elefantes/fisiología , Sonido , Ballenas/fisiología , Animales , Cóclea/anatomía & histología , Cóclea/fisiología
4.
J Intern Med ; 267(1): 54-70, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20059644

RESUMEN

Cell sheet technology (CST) is based on the use of thermoresponsive polymers, poly(N-isopropylacrylamide) (PIPAAm). The surface of PIPAAms is formulated in such a way as to make its typical thickness <100 nm. In this review, we first focus on how the methods of PIPAAm-grafted surface preparations and functionalization are important to be able to harvest a functional cell sheet, to be further transplanted. Then, we present aspects of tissue mimics and three-dimensional reconstruction of a tissue in vitro. Finally, we give an overview of clinical applications and clinically relevant animal experimentations of the technology, such as cardiomyopathy, visual acuity, periodonty, oesophageal ulcerations and type 1 diabetes.


Asunto(s)
Técnicas de Cultivo de Célula/métodos , Ingeniería de Tejidos/métodos , Animales , Materiales Biocompatibles , Cardiomiopatías/terapia , Adhesión Celular , Células Cultivadas , Enfermedades de la Córnea/terapia , Diabetes Mellitus Tipo 1/terapia , Enfermedades del Esófago/terapia , Humanos , Membranas Artificiales , Nanotecnología , Ratas , Medicina Regenerativa/métodos , Propiedades de Superficie
5.
Exp Eye Res ; 87(3): 191-6, 2008 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-18644592

RESUMEN

Cultivated oral mucosal epithelial sheet transplantation is a new surgical strategy to treat severe ocular surface disorders such as chemical burns, ocular cicatricial pemphigoid, and Stevens-Johnson syndrome. MUC16 is thought to be the most important membrane-associated mucin on the ocular surface because it forms a protective barrier on the epithelial cell surface. In this study, we studied MUC16 expression in mRNA and protein levels and compared the expression patterns between cultivated oral mucosal epithelial cell sheet and oral mucosal tissue. Specimens (5x5 mm) of oral mucosal tissue harvested from healthy volunteers were used. The oral mucosal epithelial cells were cultured on temperature-responsive culture dishes to generate stratified cell sheets. Cultivated oral mucosal epithelial cells formed three- to five-cell thick stratified sheets for 2 weeks. Scanning electron micrographs revealed that the apical surfaces of the oral mucosal tissue and the oral mucosal sheets were covered with dense microvilli/microplicae. Real-time PCR showed significantly more MUC16 transcripts in the cultivated oral mucosal sheets and corneal epithelial sheets than in the oral mucosal tissue (P=0.023 and 0.008, respectively, Mann-Whitney rank sum test). These findings were confirmed by immunohistochemical examination using an MUC16 antibody to the protein. MUC16 protein was localized to the apical cells of the oral mucosal sheets, but the human oral mucosal tissue did not express MUC16 protein in any cell layers. In this study, interestingly, the expression of membrane-associated mucin MUC16 differs between human oral mucosal epithelia and cultivated epithelial sheets. MUC16 expressed in the oral mucosal sheets may contribute to ocular surface reconstruction after oral mucosal sheet transplantation.


Asunto(s)
Antígeno Ca-125/metabolismo , Proteínas de la Membrana/metabolismo , Mucosa Bucal/metabolismo , Antígeno Ca-125/genética , Técnicas de Cultivo de Célula , Células Epiteliales/metabolismo , Epitelio Corneal/anatomía & histología , Humanos , Proteínas de la Membrana/genética , Microscopía Electrónica de Rastreo , Mucosa Bucal/ultraestructura , Reacción en Cadena de la Polimerasa/métodos , ARN Mensajero/genética
6.
J Periodontal Res ; 43(3): 364-71, 2008 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-18205734

RESUMEN

BACKGROUND AND OBJECTIVE: In the present study we evaluated if a multilayered human periodontal ligament cell sheet could reconstruct the physiological architecture of a periodontal ligament-cementum complex. MATERIAL AND METHODS: Human periodontal ligament cells were isolated and then cultured in dishes coated with a temperature-responsive polymer to allow cell detachment as a cell sheet. In the control group, human periodontal ligament cells were cultured in Dulbecco's modified Eagle's minimal essential medium containing 10% fetal bovine serum and 1% antibiotics. In the experimental group, human periodontal ligament cells were cultured in Dulbecco's modified Eagle's minimal essential medium and osteodifferentiation medium containing dexamethasone, ascorbic acid and beta-glycerophosphate. After 3 wk, scanning electron microscopy was carried out, in addition to staining for alkaline phosphatase activity and for calcium (using the Von Kossa stain). Then human periodontal ligament cell sheets were multilayered and placed onto dentin blocks. The constructs were transplanted subcutaneously into the back of immunodeficient rats. At 1 and 6 wk after transplantation, the animals were killed. Demineralized tissue sections were stained using hematoxylin and eosin, and Azan, and then analyzed. RESULTS: After 3 wk of culture in osteodifferentiation medium, human periodontal ligament cells produced mineral-like nodules and also showed positive staining for alkaline phosphatase, calcium (Von Kossa) and mRNA expression of type I collagen. By contrast, in the control group only weak alkaline phosphatase staining was observed, the Von Kossa stain was negative and there was no mRNA expression of type I collagen. Six weeks after transplantation with human periodontal ligament cells cultured in osteodifferentiation medium, most of the dentin surfaces showed a newly immature cementum-like tissue formation and periodontal ligament with perpendicular orientation inserted into the newly deposited cementum-like tissue. CONCLUSION: This study suggests that the multilayered temperature-responsive culture system can be used as a novel strategy for periodontal regeneration. The human periodontal ligament cell sheet technique may be applicable for regeneration of the clinical periodontal ligament-cementum complex.


Asunto(s)
Dentina/trasplante , Ligamento Periodontal/citología , Ligamento Periodontal/trasplante , Regeneración , Ingeniería de Tejidos/métodos , Animales , Técnicas de Cultivo de Célula , Células Cultivadas , Medios de Cultivo , Cemento Dental/trasplante , Electroforesis en Gel de Poliacrilamida/métodos , Humanos , Ligamento Periodontal/fisiología , Ratas , Ratas Endogámicas F344 , Ratas Desnudas , Temperatura , Andamios del Tejido
7.
Int J Artif Organs ; 30(6): 495-500, 2007 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-17628850

RESUMEN

Transplantation of mesothelial cells is used to repair peritoneum that is damaged by surgery, peritonitis, and peritoneal dialysis. The largest obstacle for clinical application of mesothelial cell transplantation is the lack of a reliable source of mesothelial cells. So far, they are isolated from omentum, mesentery, parietal wall and ascites. Procedures used to obtain mesothelial cells from the omentum or mesentery are invasive, however, especially in pre-operative situations. Sufficient amounts of ascites for aspiration can not be obtained under physiological conditions. We have developed a novel method of isolating mesothelial cells from the tunica vaginalis. The tunica vaginalis originates from the peritoneum and descends into the scrotum along with the testis during fetal development. This region provides a source of mesothelial cells that is convenient to approach and free from abdominal complications. Transplantation of autologous mesothelial cells that were isolated from tunica vaginalis was effective in preventing post-operative adhesions. In this review, we summarize mesothelial cell transplantation trials and describe the method of isolating mesothelial cells form the tunica vaginalis. Mesothelial cell transplantation might be widely accepted for clinical use in the near future.


Asunto(s)
Células Epiteliales/trasplante , Epitelio/trasplante , Peritoneo/patología , Testículo/ultraestructura , Animales , Separación Celular , Células Cultivadas , Perros , Masculino , Diálisis Peritoneal Ambulatoria Continua/efectos adversos , Peritonitis/complicaciones , Regeneración/fisiología , Adherencias Tisulares/prevención & control , Trasplante Autólogo
8.
Eur Cell Mater ; 10: 23-30; discussion 23-30, 2005 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-16088852

RESUMEN

We used temperature-responsive culture dishes onto which the temperature-responsive polymer, poly(Nisopropylacrylamide), was covalently grafted for tissue engineering. Confluent cells harvested as intact sheets from these surfaces by simple temperature reduction can be transferred to various surfaces including additional culture dishes, other cell sheets, and tissues. In order to examine the maintenance of cell polarity, Madin-Darby canine kidney cells and human primary renal proximal tubule epithelial cells which had developed apical-basal cell polarity in culture, were subjected to cell sheet transfer. This functional and structural cell polarity, which is susceptible to treatment with trypsin, was examined by immunohistochemistry and transmission electron microscopy. Using our cell-sheet method, the noninvasive transfer of these cell sheets retaining typical distributions of Na+/K+-ATPase, GLUT-1, SGLT-1, aquaporin-1, neutral endopeptidase and dipeptidylendopeptidase IV, could be achieved. The transferred cell sheets also developed numerous microvilli and tight junctions at the apical and lateral membranes, respectively. For biochemical analysis, immunoblotting of occludin, a transmembrane protein that composes tight junctions, was conducted and results confirmed that occludin remained intact after cell sheet transfer. This two-dimensional cell sheet manipulation method promises to be useful for tissue engineering as well as in the investigation of epithelial cell polarity.


Asunto(s)
Técnicas de Cultivo de Célula/instrumentación , Técnicas de Cultivo de Célula/métodos , Polaridad Celular , Células Epiteliales/citología , Túbulos Renales Proximales/citología , Temperatura , Animales , Células Cultivadas , Perros , Células Epiteliales/ultraestructura , Humanos , Immunoblotting , Ingeniería de Tejidos/instrumentación , Ingeniería de Tejidos/métodos
9.
Lab Anim ; 49(2): 172-6, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25448868

RESUMEN

Dental pulp is a potential source of cells that can be used in cell replacement therapy for various nerve disorders, including stroke, spinal cord injury, and peripheral nerve defect. However, the validation of an animal model closely related to humans is needed in translational research. The miniature pig is a suitable experimental model in maxillofacial surgery, because its anatomical structure and size are similar to those of humans. However, the swine tooth is extremely long. The routine closed extraction procedure for harvesting dental pulp tissue causes root fracture. This report describes the details of a surgical procedure for tooth extraction. Four healthy 7-8-month-old male NIBS miniature pigs were used. Two mandibular deciduous right incisors (Di1 and Di2) were extracted in order to obtain dental pulp tissue. Gingival envelope incision with vertical-releasing incision was performed, and a full-thickness mucoperiosteal flap was made. The buccal alveolar bone was exposed and removed by osteotomy. Di1 and Di2 were extracted. Dental pulp tissue was obtained from these extracted teeth by splitting hard tissue. In this procedure, 9.8 ± 2.5 × 10(5) cells were obtained from the mandibular Di1 and Di2 (n = 4).


Asunto(s)
Pulpa Dental , Incisivo/cirugía , Medicina Regenerativa/métodos , Extracción Dental/métodos , Diente Primario/cirugía , Anestesia Intravenosa , Animales , Masculino , Modelos Animales , Porcinos , Porcinos Enanos , Investigación Biomédica Traslacional
10.
Free Radic Res ; 49(8): 1038-47, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25968953

RESUMEN

Methamphetamine (METH)-induced neurotoxicity is associated with mitochondrial dysfunction and enhanced oxidative stress. The aims of the present study conducted in the mouse brain repetitively treated with METH were to (1) examine the redox status using the redox-sensitive imaging probe 3-methoxycarbonyl-2,2,5,5-tetramethylpiperidine-1-oxyl (MCP) and (2) non-invasively visualize the brain redox status with electron paramagnetic resonance (EPR) imaging. The rate of reduction of MCP was measured from a series of temporal EPR images of mouse heads, and this rate was used to construct a two-dimensional map of rate constants called a "redox map." The obtained redox map clearly illustrated the change in redox balance in the METH-treated mouse brain that is a known result of oxidative damage. Biochemical assays also showed that the level of thiobarbituric acid-reactive substance, an index of lipid peroxidation, was increased in mouse brains by METH. The enhanced reduction in MCP observed in mouse brains was remarkably suppressed by treatment with the dopamine synthase inhibitor, α-methyl-p-tyrosine, suggesting that enhancement of the reduction reaction of MCP resulted from enzymatic reduction in the mitochondrial respiratory chain. Furthermore, magnetic resonance imaging (MRI) of METH-treated mice using a blood-brain barrier (BBB)-impermeable paramagnetic contrast agent revealed BBB dysfunction after treatment with METH for 7 days. MRI also indicated that the impaired BBB recovered after withdrawal of METH. EPR imaging and MRI are useful tools not only for following changes in the redox status and BBB dysfunction in mouse brains repeatedly administered METH, but also for tracing the drug effect after withdrawal of METH.


Asunto(s)
Barrera Hematoencefálica/efectos de los fármacos , Estimulantes del Sistema Nervioso Central/toxicidad , Metanfetamina/toxicidad , Estrés Oxidativo , Animales , Barrera Hematoencefálica/metabolismo , Encéfalo/irrigación sanguínea , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Permeabilidad Capilar/efectos de los fármacos , Medios de Contraste/farmacocinética , Espectroscopía de Resonancia por Spin del Electrón , Peroxidación de Lípido , Locomoción/efectos de los fármacos , Imagen por Resonancia Magnética , Masculino , Ratones Endogámicos C57BL , Óxidos de Nitrógeno/farmacocinética , Compuestos Organometálicos/farmacocinética , Oxidación-Reducción
11.
J Tissue Eng Regen Med ; 9(1): 24-30, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23165985

RESUMEN

The authors aimed to repair and regenerate articular cartilage with layered chondrocyte sheets, produced using temperature-responsive culture dishes. The purpose of this study was to investigate the humoral factors produced by layered chondrocyte sheets. Articular chondrocytes and synovial cells were harvested during total knee arthroplasty. After co-culture, the samples were divided into three groups: a monolayer, 7 day culture sheet group (group M); a triple-layered, 7 day culture sheet group (group L); and a monolayer culture group with a cell count identical to that of group L (group C). The secretion of collagen type 1 (COL1), collagen type 2 (COL2), matrix metalloproteinase-13 (MMP13), transforming growth factor-ß (TGFß), melanoma inhibitory activity (MIA) and prostaglandin E2 (PGE2) were measured by enzyme-linked immunosorbent assay (ELISA). Layered chondrocyte sheets produced the most humoral factors. PGE2 expression declined over time in group C but was significantly higher in groups M and L. TGFß expression was low in group C but was significantly higher in groups M and L (p<0.05). Our results suggest that the humoral factors produced by layered chondrocyte sheets may contribute to cartilaginous tissue repair and regeneration.


Asunto(s)
Condrocitos/citología , Inmunidad Humoral/fisiología , Membrana Sinovial/citología , Adulto , Anciano , Anciano de 80 o más Años , Artroplastia de Reemplazo de Rodilla , Cartílago Articular/citología , Técnicas de Cultivo de Célula , Técnicas de Cocultivo , Medios de Cultivo , Dinoprostona/metabolismo , Ensayo de Inmunoadsorción Enzimática , Humanos , Ensayo de Materiales , Microscopía Electrónica de Rastreo , Persona de Mediana Edad , Temperatura , Factor de Crecimiento Transformador beta/metabolismo
12.
FEBS Lett ; 238(1): 116-8, 1988 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-3049155

RESUMEN

A gene encoding cystatin alpha has been chemically synthesized, cloned and expressed in E. coli. The gene of 318 base pairs was assembled by enzymatic ligation of 19 oligonucleotides and cloned into a pBR322-derived expression plasmid down stream of the tac promoter. The expression product of the synthetic gene has been purified by Sephadex G-50 column chromatography and shown to have the same properties as those of the authentic protein isolated from rat epidermis.


Asunto(s)
Escherichia coli/genética , Genes Sintéticos , Genes , Inhibidores de Proteasas/genética , Secuencia de Aminoácidos , Secuencia de Bases , Clonación Molecular , Inhibidores de Cisteína Proteinasa , Humanos , Datos de Secuencia Molecular , Plásmidos , Regiones Promotoras Genéticas , Transcripción Genética
13.
Mech Ageing Dev ; 67(1-2): 149-58, 1993 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-8469027

RESUMEN

We examined the effects of population doubling levels on collagen gel contraction by human lung fibroblasts (TIG-1). The sizes of gels at day 4 of culture, when the number of cells was the same as the initial number, were smaller with young cells than with aged cells. Therefore, retractive force had decreased with in vitro cellular aging. On the other hand, the lag time until gel contraction began became shorter with aging, resulting in the cross-over of contraction curves of young and aged cells. Morphological changes, such as pseudopodia protrusion, were suppressed in collagen gel. The surrounding collagen fibrils prevented young cells from moving more than aged cells. The weakened omnidirectional interaction with collagen fibrils on the entire surface of aged cells might result in an earlier occurrence of morphological change and, thereby, gel contraction.


Asunto(s)
Colágeno/metabolismo , Fibroblastos/metabolismo , División Celular , Células Cultivadas , Senescencia Celular/fisiología , Medios de Cultivo , Fibroblastos/citología , Geles , Humanos , Pulmón/citología , Pulmón/metabolismo
14.
J Med Chem ; 29(7): 1202-5, 1986 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-3806570

RESUMEN

As part of a study on the antitumor activities of tropolone derivatives prepared from hinokitiol, which naturally occurs in the plants of Chamaecyparis species, effects of aromatic substituents of alpha,alpha-bis(7-hydroxy-5-isopropyltropon-2-yl)toluenes on the activity were examined. Several of the compounds showed high potency in the P388 leukemia assay. 4-Hydroxy analogue 4d showed the most potent activity (T/C = 195%) at a 5 mg/kg dose. The introduction of large-size substituents, of which the steric influence prevents coplanarity of the substituted aromatic function, resulted in a remarkable decrease in the potency. X-ray structural analysis of highly potent 4-methoxy analogue 4b was undertaken.


Asunto(s)
Antineoplásicos , Cicloheptanos/síntesis química , Tropolona/síntesis química , Animales , Evaluación Preclínica de Medicamentos , Humanos , Indicadores y Reactivos , Células KB , Leucemia P388/tratamiento farmacológico , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Ratones , Relación Estructura-Actividad , Tropolona/análogos & derivados , Tropolona/uso terapéutico
15.
J Med Chem ; 27(12): 1749-53, 1984 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-6502608

RESUMEN

Treatment of tropolones with benzaldehyde diethyl acetals gave monotropolone (12) and bistropolone (13) derivatives at the benzylic position, whereas the related 1-ethoxyisochroman and the diethyl acetals of crotonaldehyde and cinnamaldehyde gave only the monotropolone derivatives (5, 10, or 11). The monotropolone derivatives (5, 10, 11, and 12) had poor potency against P388 leukemia in mice, but the bistropolone derivatives (13 and 14) showed significant potency and prolongation of life.


Asunto(s)
Antineoplásicos/síntesis química , Cicloheptanos/síntesis química , Tropolona/síntesis química , Animales , Carcinoma , División Celular/efectos de los fármacos , Línea Celular , Supervivencia Celular/efectos de los fármacos , Evaluación Preclínica de Medicamentos , Humanos , Indicadores y Reactivos , Leucemia P388/tratamiento farmacológico , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Ratones , Ratones Endogámicos , Neoplasias de la Boca , Relación Estructura-Actividad , Tropolona/análogos & derivados , Tropolona/toxicidad
16.
J Med Chem ; 24(2): 194-8, 1981 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-6162958

RESUMEN

Two types of 1'-alkylspiro[isochroman-3,4-piperidines] and 1'-alkylspiro[isochroman-4,4'-piperidines] were prepared and examined for their biological activity. Several of the compounds inhibited the compound 48/80 induced histamine release from isolated rat peritoneal mast cells. The structural requirements for this activity in the present series are discussed.


Asunto(s)
Liberación de Histamina/efectos de los fármacos , Piperidinas/síntesis química , Compuestos de Espiro/síntesis química , Animales , Fenómenos Químicos , Química , Técnicas In Vitro , Masculino , Mastocitos/metabolismo , Piperidinas/farmacología , Ratas , Compuestos de Espiro/farmacología , Relación Estructura-Actividad
17.
J Med Chem ; 30(1): 117-20, 1987 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-3806588

RESUMEN

Modifications of monotropolone 2 having poor potency against P388 in mice were studied. The alpha-ethoxy group of 2, prepared from hinokitiol and benzaldehyde diethyl acetal, was replaced with a phenolic or heteroaromatic compound by heating 2 with the appropriate nucleophile. Structure-activity relationships indicated that an acidic hydroxyl and a proton-accepting group situated in the neighboring position, which permits the formation of a chelate with a metal ion, contributed to enhanced activity. Among the compounds studied, the 8-hydroxyquinoline analogue 10f was the most favorable compound.


Asunto(s)
Antineoplásicos/síntesis química , Cicloheptanos/uso terapéutico , Leucemia P388/tratamiento farmacológico , Leucemia Experimental/tratamiento farmacológico , Tropolona/uso terapéutico , Animales , Evaluación Preclínica de Medicamentos , Espectroscopía de Resonancia Magnética , Ratones , Relación Estructura-Actividad , Tropolona/análogos & derivados
18.
J Med Chem ; 28(8): 1026-31, 1985 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-4020825

RESUMEN

Structural requirement for antitumor activity of tropolone derivatives 2-4 was explored. Isochroman derivatives (6-17, 20, and 23) and alpha, alpha-disubstituted compounds 26-30 were synthesized and their antitumor activities were tested. These nontroponoid derivatives were all inactive, implying that a tropolone ring is essential for the activity. Several compounds related to the monotropolone analogue 3 were synthesized. Among them, 31-33 showed significant activity, but their potencies were considerably weaker than those of binary tropolone analogues 4.


Asunto(s)
Antineoplásicos/síntesis química , Cicloheptanos/farmacología , Tropolona/farmacología , Animales , División Celular/efectos de los fármacos , Línea Celular , Humanos , Leucemia P388/tratamiento farmacológico , Ratones , Relación Estructura-Actividad , Tropolona/análogos & derivados , Tropolona/síntesis química
19.
J Med Chem ; 30(7): 1245-8, 1987 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-3599030

RESUMEN

As part of a study on the structure-activity relationship of antitumor-active tropolone derivatives, a series of bistropone analogues, related to potently active bistropolone 1a, were synthesized and tested for their antitumor activity in in vitro (KB cell) and in vivo (leukemia P388 in mice) systems. The methoxytropones 3 and 5, hydroxytropothione 10, and (N-methylamino)tropones 12 and 13 were inactive in both systems. Methoxytropone 6 exhibited weak activity, whose potency was equal to that of monotropolone 2a.


Asunto(s)
Antineoplásicos/síntesis química , Cicloheptanos/síntesis química , Tropolona/síntesis química , Animales , Antineoplásicos/farmacología , Ratones , Relación Estructura-Actividad , Tropolona/farmacología
20.
J Med Chem ; 35(2): 267-73, 1992 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-1732542

RESUMEN

Bistropolone derivatives (4-12) containing differing lengths of linkage between the two tropolone rings were prepared and examined for their antitumor activity in in vitro (KB cell) and in vivo (leukemia P388 in mice) systems. Parent compound 3, related compounds previously prepared, and the new compounds 4-12 were evaluated for inhibitory activity against ribonucleotide reductase by indirect means to measure their effects on the dNTP pool imbalance. Present structure-activity relationship results would suggest that potently active bistropolones in vivo inhibit intracellular ribonucleotide reductase through chelating with the two irons at the two active sites of the enzyme.


Asunto(s)
Antineoplásicos/síntesis química , Tropolona/análogos & derivados , Animales , Antineoplásicos/farmacología , Desoxirribonucleótidos/metabolismo , Leucemia P388/tratamiento farmacológico , Ratones , Relación Estructura-Actividad , Tropolona/síntesis química , Tropolona/farmacología , Células Tumorales Cultivadas/efectos de los fármacos
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