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Steroids ; 158: 108620, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32119871

RESUMO

Several drugs have been prepared to treat of heart failure using some protocols which require dangerous reagents and specific conditions. The aim of this study was to synthesize a series of steroid derivatives (compounds 2 to 18) using some chemical strategies. The biological activity of steroid derivatives against heart failure was evaluated using an ischemia/reperfusion model. In addition, the effect exerted by compounds 4 or 5 on left ventricular pressure was evaluated in the absence or presence of yohimbine, butaxamine and methoctramine. The results showed that 1) both compounds 4 or 5 significantly decrease the heart failure (translated as infarct area) compared with the compounds 2, 3 and 6-18. In addition, the compound 4 and 5 decreased the left ventricular pressure in a dose-dependent manner and this effect was significantly inhibited in the presence of methoctramine (p = 005). In conclusion, the compounds 4 or 5 decrease both the infarct area and left ventricular pressure via M2-muscarinic receptor activation.


Assuntos
Desenho de Fármacos , Insuficiência Cardíaca/tratamento farmacológico , Receptor Muscarínico M2/agonistas , Receptor Muscarínico M2/metabolismo , Esteroides/farmacologia , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Insuficiência Cardíaca/metabolismo , Masculino , Conformação Molecular , Ratos , Ratos Wistar , Esteroides/síntese química , Esteroides/química , Relação Estrutura-Atividade
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