Synthesis and Biological Activity of the Pyridine-Hexacyclic-Steroid Derivative on a Heart Failure Model

Background: Several drugs with inotropic activity have been synthesized; however, there is very little information on biological activity exerted by steroid derivatives in the cardiovascular system. Objective: The aim of this research was to prepare a steroid-pyridine derivative to evaluate the effect it exerts on left ventricular pressure and characterize its molecular interaction. Methods: The first stage was carried out through the synthesis of a steroid-pyridine derivative using some chemical strategies. The second stage involved the evaluation of the biological activity of the steroid-pyridine derivative on left ventricular pressure using a model of heart failure in the absence or presence of the drugs, such as flutamide, tamoxifen, prazosin, metoprolol, indomethacin, and nifedipine. Results: The results showed that steroid-pyridine derivative increased left ventricular pressure in a dose-dependent manner (0.001-100 nM); however, this phenomenon was significantly inhibited only by nifedipine at a dose of 1 nM. These results indicate that positive inotropic activity produced by the steroid-pyridine derivative was via calcium channel activation. Furthermore, the biological activity exerted by the steroid-pyridine derivative on the left ventricle produces changes in cAMP concentration. Conclusion: It is noteworthy that positive inotropic activity produced by this steroid-pyridine derivative involves a different molecular mechanism compared to other positive inotropic drugs. Therefore, this steroid could be a good candidate for the treatment of heart failure.

Synthesis of new azaindeno-acetonitrile derivative with inotropic activity against heart failure model

Several steroid derivatives have prepared as inotropic drugs; however, there are few reports on azaindeno-steroid derivatives with inotropic activity. The objective of this investigation was to prepare some azaindeno-acetonitrile derivatives (compounds 3 to 7) to evaluate their biological activity on left ventricular pressure. The first step was achieved by preparation of azaindeno-steroid derivatives using reactions of etherification and addition. The second stage involves the evaluation of biological activity from azaindeno-steroid derivatives on left ventricular pressure in a heart failure model using either estrone or an enone-steroid derivative (compound 2) as controls. The results showed that only compound 6 increases left ventricular pressure compared with estrone, compounds 2-5 and 6. In conclusion, the positive inotropic effect exerted by compound 6 depends on the functional groups involved in its chemical structure.