Design and synthesis of methylthiododec-5-en-7-yn-6-yl-steroid derivativewith positive inotropic activity

Abstract

There are several drugs for the treatment of heart failure; however, some of these drugs can produce several secondary effects such as hyperkalemia, arrhythmias, and others. Therefore, the aim of this study was synthesized a new methylthiododec-5-en-7-yn-6-yl-steroid derivative using some chemical strategies. In addition, the biological activity of the steroid derivative against heart failure was evaluated using an isolated heart model. Also, the effect produced by this steroid derivative on left ventricular pressure (LVP) was determinate using some positive inotropic drugs such as milrinone, digoxin, levosimedan and dobutamine as controls. The results showed that methylthiododec-5-en-7-yn-6-yl-steroid derivative increase LVP in a dose-dependent manner and this effect was like that produced by milrinone. In conclusion, the biological activity produced by steroid-derivative; 1) depends on the functional groups involved in their chemical structure; 2) could act as a positive inotropic agent similar to milrinone. All these data suggest that steroid-derivative may be a good candidate for the treatment of heart failure.