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

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

Author(s): Figueroa-Valverde Lauro*, Diaz-Cedillo Francisco, Rosas-Nexticapa Marcela*, Mateu-Armand Virginia, Garcimarero-Espino E. Alejandra, Lopez-Ramos Maria, Hau-Heredia Lenin, Borges-Ballote Yaritza and Cabrera-Tuz Jhair

Volume 19, Issue 4, 2020

Page: [393 - 412] Pages: 20

DOI: 10.2174/1871523018666191003152854

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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 differences in the chemical structure of each one of the steroid derivatives.

Objectives: The aim of this study was to synthesize a new bis-steroid-methanocyclobutanaphthalene- dione derivative using some tools chemical.

Methodology: The biological activity exerted by the bis-steroid-methanocyclobutanaphthalene- dione derivative against ischemia/reperfusion injury was evaluated in an isolated heart model using noradrenaline, milrinone, dobutamine, levosimendan, 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 decreases the ischemia-reperfusion injury translated as a decrease in the the infarct area in a similar manner to levosimendan drug; 2) both bis-steroidmethanocyclobuta- naphthalene-dione and Bay-K-8644 increase the left ventricular pressure and 3) the biological activity exerted by bis-steroid-methanocyclobuta-naphthalenedione derivative against left ventricular pressure is inhibited by nifedipine.

Conclusion: In conclusion, the bis-steroid-methanocyclobuta-naphthalene-dione derivative decreases the area of infarction and increases left ventricle pressure via calcium channels activation; this phenomenon could constitute a new therapy for ischemia/reperfusion injury.

Keywords: Infarct, ischemia, pressure, reperfusion, steroid, calcium channel.

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