Synthesis and Biological Activity of a Bis-steroid-methanocyclobuta-naphthalene-dione Derivative against Ischemia/Reperfusion Injury viaCalcium Channel Activation

Autor: Lauro, Figueroa-Valverde, Francisco, Diaz-Cedillo, Marcela, Rosas-Nexticapa, Virginia, Mateu-Armand, Alejandra, Garcimarero-Espino E., Maria, Lopez-Ramos, Lenin, Hau-Heredia, Yaritza, Borges-Ballote, Jhair, Cabrera-Tuz
Zdroj: Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry; December 2020, Vol. 19 Issue: 4 p393-412, 20p
Abstrakt: 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.
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