Activity Exerted by Fluoro-2,4-Dioxaspiro[Bicyclo[3.3.1]Indene Derivative Against Ischemia/Reperfusion Injury

Abstract

Several drugs for the treatment of heart failure; however, some of these drugs can produce some secondary effects such as arrhythmias and hypercalcemia and others. The aim of this investigation was to evaluate the biological activity of a Fluoro-2,4dioxaspiro[bicyclo[3.3.1]indene derivative against both infarct area and left ventricular pressure. The effect exerted of a Fluoro-2,4dioxaspiro[bicyclo[3.3.1]indene derivative against both infarct area and left ventricular pressure was evaluated in an ischemia/reperfusion model using indomethacin and ramatroban as a control. Furthermore, a theoretical study was carried out to determine the interaction of Fluoro-2,4dioxaspiro[bicyclo[3.3.1]indene derivative with COX-1, COX-2, and thromboxane A2 using the 5u6x, 3ntg, and 6iiu proteins as controls. The results showed that Fluoro-2,4dioxaspiro[bicyclo[3.3.1]indene derivative decrease the infarct and left ventricular pressure; however, this effect was inhibited in the presence of ramatroban. In addition, other data indicated that Fluoro-2,4dioxaspiro[bicyclo[3.3.1]indene derivative could interact with both COX-2 and thromboxane A2 protein surface. All these data indicate that the biological activity of Fluoro-2,4dioxaspiro[bicyclo[3.3.1]indene derivative against infarct area and left ventricular pressure was via both COX-2 and thromboxane A2 inhibition. Therefore, this compound could be s candidate for the treatment of heart failure.