RESUMO
A novel naturally occurring compound with a benzofuran skeleton was isolated from a plant, Tephrosia purpurea collected in Bangladesh. The chemical synthesis of this compound confirmed its structure, and preliminary biological results showed its suppressive activity towards histamine H1 gene expression. One isomer and four derivatives were also synthesized, and their suppression activity was investigated. Although only small quantities of this compound can be isolated from its natural source, a 10 g scale synthesis was demonstrated by the newly developed method.
Assuntos
Benzofuranos/química , Receptores Histamínicos H1/metabolismo , Tephrosia/química , Antialérgicos/síntese química , Antialérgicos/química , Antialérgicos/farmacologia , Benzofuranos/isolamento & purificação , Benzofuranos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Células HeLa , Humanos , Isomerismo , Componentes Aéreos da Planta/química , Componentes Aéreos da Planta/metabolismo , Receptores Histamínicos H1/genética , Tephrosia/metabolismoRESUMO
Synthesis of four water-soluble resveratrol and piceatannol derivatives bearing symmetrically branched glyceryl trimer (BGL003) with a non-biocleavable linkage, and their biological evaluation as a mitochondrial fusion-inducing agent with cellular fat-reducing effect from cells, is described. The effect of Piceatannol-BGL003 conjugate was as high as that of original stilbenoids.
Assuntos
Glicerol/química , Estilbenos/química , Glicerol/síntese química , Mitocôndrias/metabolismo , Resveratrol , Solubilidade , Estilbenos/síntese química , Água/químicaRESUMO
Four kinds of symmetrically branched oligoglyceryl trimeric (BGL003)-paclitaxel conjugates and a corresponding heptameric (BGL007) conjugate were synthesized. Molecular weights of all the compounds were less than two times that of paclitaxel. The anti-tumor activity of the most water-soluble BGL003 conjugate was examined and found to be preserved in spite of the chemical modification that is displacement of the N3'-debenzoyl residue with the BGL003 succinyl residue.
Assuntos
Antineoplásicos Fitogênicos/síntese química , Antineoplásicos Fitogênicos/farmacologia , Glicerol/química , Glicerol/farmacologia , Neoplasias Experimentais/tratamento farmacológico , Paclitaxel/química , Paclitaxel/farmacologia , Animais , Antineoplásicos Fitogênicos/química , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Conformação Molecular , Peso Molecular , Solubilidade , Relação Estrutura-Atividade , Ensaios Antitumorais Modelo de XenoenxertoAssuntos
Doses de Radiação , Monitoramento de Radiação/normas , Sistemas de Informação em Radiologia , Sistema de Registros , Gestão da Segurança/normas , Tomografia Computadorizada por Raios X/instrumentação , Tomografia Computadorizada por Raios X/normas , Tamanho Corporal , Simulação por Computador , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Método de Monte Carlo , Monitoramento de Radiação/métodos , SoftwareRESUMO
An 80-year-old man, who had been taking the antiarrhythmic drug amiodarone for chronic atrial fibrillation since October 2004, developed dyspnea and fever in June 2005, and was admitted to our hospital. Chest X-ray and CT scan showed ground-glass opacities in all lung fields. Arterial blood gas analysis revealed hypoxemia. These findings led to a diagnosis of acute respiratory distress syndrome. Oral amiodarone was discontinued, and steroid pulse therapy was started; however, the disease progressed rapidly, and the patient died on the fourth hospital day. Autopsy showed diffuse alveolar damage, accumulation of edema fluid in the alveolar spaces, and the presence of foamy macrophages, leading to a diagnosis of amiodarone-induced pulmonary damage.
Assuntos
Amiodarona/efeitos adversos , Antiarrítmicos/efeitos adversos , Síndrome do Desconforto Respiratório/induzido quimicamente , Idoso de 80 Anos ou mais , Fibrilação Atrial/tratamento farmacológico , Doença Crônica , Humanos , Masculino , Síndrome do Desconforto Respiratório/patologiaRESUMO
Head-to-head bis(alpha-pyridonato)-bridged bis(ethylenediamine)dipalladium(ii), HH-[Pd(2)(en)(2)(alpha-pyridonato)(2)](ClO(4))(2), was synthesized and structurally characterized by X-ray crystallography. The (1)H NMR spectra show that the head-to-head (HH) dimer produces the head-to-tail (HT) dimer and monomers ([Pd(en)(alpha-pyridone)(2)](2+), [Pd(en)(H(2)O)(alpha-pyridone)](2+), [Pd(en)(H(2)O)(2)](2+), etc.) in aqueous solution, and the relative amount of dimers to monomers is dependent on the total concentration of the HH dimer dissolved as well as the acidity of the solution. It was found that the formation of the HH and HT dimers from the monomers is fast, and the HT dimer is produced from the HH dimer only via coexisting monomers, i.e., there is no direct isomerization path between the HH and HT dimers. The kinetic analyses for the HH <==>HT isomerization reaction with time-resolved (1)H NMR measurements revealed that the reaction proceeds via first-order kinetics, which was explained based on a relaxation process. The rate determining step for HH <==>HT isomerization is the reaction step between the mono-alpha-pyridone complex and the bis-alpha-pyridone complex, [Pd(en)(H(2)O)(alpha-pyridone)](2+)+alpha-pyridone <==> [Pd(en)(alpha-pyridone)(2)](2+).