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

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.

Biological Activity of a 4-Hydroxy-Furanyl-Benzamide Derivative on Heart Failure.

BACKGROUND: There are studies that suggest that some benzamide derivatives may exert effects on heart failure; however, their molecular mechanism is not very clear. OBJECTIVE: The aim of this research was to evaluate the biological activity of a 4-hydroxy-furanyl-benzamide derivative against heart failure translated as area infarct. METHODS: Biological activity produced by 4-hydroxy-furanyl-benzamide derivative against heart failure was determinate using an ischemia-reperfusion injury model. In addition, the effects exerted by the 4-hydroxy-furanyl-benzamide derivative on left ventricular pressure (LVP) was evaluated in the absence or presence of some drugs such as yohimbine, butaxamine, methoctramine and L-NAME using a model of rat heart isolated. RESULTS: The results showed that 4-hydroxy-furanyl-benzamide derivative decrease both infarct area and LVP. However, the effect produced by 4-hydroxy-furanyl-benzamide derivative on LVP was inhibited in the presence of both methoctramine and L-NAME. CONCLUSIONS: All these data suggest that biological activity produced by 4-hydroxy-furanyl-benzamide derivative on left ventricular pressure is through of both M2-muscarinic receptor and nitric oxide synthase enzyme activation. It is important to mention that this phenomenon results as a decrease of both infarct area and heart failure.

Evaluation of Biological Activity of a Diazocine Derivative against Heart Failure Using an Ischemia-Reperfusion Injury Model.

BACKGROUND: There are studies, which suggest that some diazocine derivatives can exert effects on the cardiovascular system; however, these effects are not very clear. OBJECTIVE: The aim of this research was to evaluate the biological activity of a diazocine derivative against heart failure translated as area infarct. METHODS: Biological activity produced by diazocine derivatives against heart failure was determinate using an ischemia/reperfusion injury model. Besides, to characterize the molecular mechanism of effect exerted by diazocine derivative on left ventricular pressure (LVP) was determinate in an isolated rat heart model using nifedipine, PINAME TXA2, and quinalizarin as controls. RESULTS: The results showed that diazocine derivative decrease the infarct area and increase the LVP. However, the effect produced by diazocine derivative on LVP was inhibited in the presence of quinalizarin. CONCLUSIONS: The results indicate that biological activity produced by diazocine derivative on left ventricular pressure is through protein CK2 activation; this phenomenon could be translated as a decrease in both infarct area and heart failure.

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.