Design and synthesis of two new steroid derivatives with biological activity on heart failure via the M-muscarinic receptor activation.

Abstract

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 M-muscarinic receptor activation.