RESUMO
In this paper a straightforward synthesis of a novel pyrazole derivative is reported. Prominent feature of this synthetic process is a 1,3-Dipolar Cycloaddition of a suitable nitrile imine with an activated α,ß-unsaturated lactam to afford directly and regioselectively the corresponding ring-fused pyrazole. Having obtained the central core of the synthetic target, a double stepwise functionalization with a "side chain" characterized by a terminal cyclic aliphatic amine was carried out. This molecular structure was designed to interact strongly with typical biological residues, and indeed it showed potent anticancer capability: in vitro cytotoxicity test on five different cancer cell lines showed interesting IC50 values in the range of 15-60 µM for exposure time of 24-72 h, thus resulting comparable with commercially available and nowadays therapeutically exploited anticancer compounds, such as 5-FU and NVP-BEZ235.
Assuntos
Antineoplásicos/síntese química , Pirazóis/síntese química , Aminoácidos Cíclicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Reação de Cicloadição , Desenho de Fármacos , Humanos , Iminas/química , Lactamas/química , Nitrilas/química , Pirazóis/farmacologiaRESUMO
The action of the most common diuretics is reviewed with emphasis on precise indications in the case of cardiac deficiency, arterial hypertension and certain forms of angina pectoris. These drugs are judged extremely useful if the necessary precautions are taken at all times. Disturbances to the water-electrolyte balance may however occur during treatment and changes in the magnesium electrolyte are described in the light of recent developments in our knowledge of the physiopathology of diuretics.
Assuntos
Angina Pectoris/tratamento farmacológico , Diuréticos/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Hipertensão/tratamento farmacológico , Doença Cardiopulmonar/tratamento farmacológico , Glicosídeos Digitálicos/uso terapêutico , Interações Medicamentosas , Humanos , Deficiência de Magnésio/induzido quimicamente , Deficiência de Potássio/induzido quimicamente , Equilíbrio Hidroeletrolítico/efeitos dos fármacosRESUMO
Blood pressure levels and related factors such as age, sex, body mass index, socioeconomic level and family were studied in a group of 398 young subjects. A high incidence of subjects with borderline hypertension was confirmed. The results analysed and discussed the conclusion being reached that the form of arterial hypertension may be considered as either the onset or at least a risk factor or stable hypertension.
