Evaluation of Biological Activity Exerted by an Aza-bicyclocarboxylic acid Derivative using Anischemia-Reperfusion Injury Model

Abstract

The main objective of this study was to evaluate the biological activity of a new compound (derived from aza-bicyclo-carboxylic acid) against heart failure caused by the ischemia- reperfusion phenomenon. In addition, to characterize de molecular mechanism involved in the effect exerted by aza-bicyclo-carboxylic acid against infarction area, some drugs such as prazosin, metoprolol, propanolol, tamoxifen, flutamide, finasteride, nifedipine, levosimedan, adenosine, rolofylline, isoproterenol and the compound ZM-241385 were used as pharmacological tools. The data found indicated that biological activity induced by compound 3 on infarction area only was similar at effect exerted by adenosine; however, the effect produced by compound 3 was blocked with of rolofylline. Other data showed that the biological activity of compound 3 decreases the cAMP levels in a time-dependent manner. In conclusion, the results indicate that compound 3 can produce a cardioprotective effect against myocardial ischemia-reperfusion injury translated as a decrease on infarction area; this phenomenon involves A1-adenosine receptor activation and, as a result may cause changes in cAMP levels.

Synthesis of two indomethacin‐dimers with biological activity on heart failure

“…*Krebs-Henseleit solution was prepared using a previously technique reported. [17] intraperitoneally (50 mg/kg body weight). After induction of anesthesia, an abdominal thoracic laparotomy was performed on the animals to remove the heart.…”

“…Congestive heart failure developed using a previously protocol reported; [17] in this sense, the hearts were perfused with the Krebs-Henseleit solution for 15 min to balance their biological activity. Then, the hearts underwent a period of ischemia for 40 minutes due to closure of the perfusion system in the absence (control) or in presence of each of drug.…”

“…2) The administered dose (0.001 nM] was based on previous methods reported for compounds that have effects on heart failure; [17] 3) Then, the hearts were cut into two sections to determine the infarct area using a previously reported protocol. [18]…”