کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1357809 981283 2015 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Cardiovascular activity of the chiral xanthone derivatives
ترجمه فارسی عنوان
فعالیت قلب و عروق مشتقات کراتین زانتون
کلمات کلیدی
ضد آرتریت، هیپوتانسی آدرنرژیک کسانتون، سنتز
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
چکیده انگلیسی

A series of 6 derivatives of xanthone were synthesized and evaluated for cardiovascular activity. The following pharmacological experiments were conducted: the binding affinity for adrenoceptors, the influence on the normal electrocardiogram, the effect on the arterial blood pressure, the effect on blood pressor response and prophylactic antiarrhythmic activity in adrenaline induced model of arrhythmia (rats, iv). Two compounds revealed nanomolar affinity for α1-adrenoceptor which was correlated with the strongest cardiovascular (antiarrhythmic and hypotensive) activity in animals’ models. They were enantiomers of previously described (R,S)-4-(2-hydroxy-3-(4-(2-methoxyphenyl)piperazin-1-yl)propoxy)-9H-xanthen-9-one hydrochloride and revealed similar antiarrhythmic potential in adrenaline induced model of arrhythmia in rats after intravenous injection (ED50 = 0.53 mg/kg and 0.81 mg/kg, respectively). These values were lower than values obtained for reference drug urapidil. These compounds were more active in this experiment than urapidil (ED50 = 1.26 mg/kg). The compound 5 administered iv at doses of 0.62–2.5 mg/kg at the peak of arrhythmia prevented and/or reduced the number of premature ventricular beats in a statistically significant manner. The ED50 value was 1.20 mg/kg. The S-enantiomer (6) given at the same doses did not show therapeutic antiarrhythmic activity in this model.These compounds significantly decreased the systolic and diastolic blood pressure throughout the whole observation period in anesthetized, normotensive rats. The studied enantiomers showed higher toxicity than urapidil, but imperceptibly higher that another cardiovascular drugs, that is, carvedilol or propranolol. They were also evaluated for mutagenic potential in the Ames (Salmonella) test. It was found that at the concentrations tested the compounds were non mutagenic when compared to solvent control.Results were quite promising and suggested that in the group of xanthone derivatives new potential antiarrhythmics and hypotensives might be found.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 23, Issue 20, 15 October 2015, Pages 6714–6724
نویسندگان
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