Effect Produced by a Cyclooctyne Derivative on Both Infarct Area and Left Ventricular Pressure via Calcium Channel Activation

Abstract

Background: There are reports which indicate that some cyclooctyne derivatives may exert changes in cardiovascular system; however, its molecular mechanism is not very clear.

Objective: The aim of this study was to evaluate the biological activity of four cyclooctyne derivatives (compounds 1: to 4: ) produced on infarct area and left ventricular pressure.

Methods: Biological activity produced by cyclooctyne derivatives on infarct area was determinate using an ischemia/reperfusion injury model. In addition, to characterize the molecular mechanism of this effect, the following strategies were carried out as follows; i) biological activity produced by cyclooctyne derivative (compound 4: ) on either perfusion pressure or left ventricular pressure was evaluated using an isolated rat heart; ii) theoretical interaction of cyclooctyne derivative with calcium channel (1t0j protein surface) using a docking model.

Results: The results showed that cyclooctyne derivative (compound 4: ) decrease infarct area of in a dose-dependent manner compared with compound 1: to 3: . Besides, this cyclooctyne derivative increase both perfusion pressure and left ventricular pressure which was inhibited by nifedipine. Other theoretical data suggests that cyclooctyne derivative could interact with some aminoacid residues (Met₈₃, Ile₈₅, Ser₈₆, Leu₁₀₈, Glu₁₁₄) involved in 1t0j protein surface.

Conclusions: All these data indicate that cyclooctyne derivative increase left ventricular pressure via calcium channel activation and this phenomenon could be translated as a decrease of infarct area.