Synthesis and Biological Activity of a Bis-steroid-methanocyclobutanaphthalene- dione Derivative against Ischemia/Reperfusion Injury via Calcium Channel Activation

Abstract

Background: There is some experimental data on the effect exerted by some steroid derivatives against ischemia/reperfusion injury; however, the molecular mechanism is very confusing, perhaps this phenomenon could be due to the protocols used and/or to differences in the chemical structure of each one of the steroid derivatives. Objective: The aim of this study was synthesizing a new bis-steroid-methanocyclobuta-naphthalene-dione derivative using some tools chemical. Methodology: The biological activity exerted by the bis-steroid-methanocyclobuta-naphthalene-dione derivative against ischemia/reperfusion injury was evaluated in an isolated heart model using noradrenaline, milrinone, dobutamine, levosimedan, and Bay-K-8644 as controls. In addition, other alternative experiments were carried out to evaluate the biological activity induced by the bis-steroid-methanocyclobuta-naphthalene-dione derivative against left ventricular pressure in the absence or presence of nifedipine. Results: The results showed that 1) the bis-steroid-methanocyclobuta-naphthalene-dione derivative significantly decrease the ischemia-reperfusion injury translated as decrease the infarct area in a similar manner that levosimedan drug; 2) both bis-steroid-methanocyclobuta-naphthalene-dione and Bay-K-8644 increase the left ventricular pressure and 3) the biological activity exerted by bis-steroid-methanocyclobuta-naphthalene-dione derivative against left ventricular pressure was inhibited by nifedipine. Conclusion: The bis-steroid-methanocyclobuta-naphthalene-dione derivative decreases the area of infarction and increase left ventricle pressure via calcium channels activation; this phenomenon could constitute a new therapy for ischemia/reperfusion injury.