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Natural Guanine Derivatives Exert PARP-Inhibitory and Cytoprotective Effects in a Model of Cardiomyocyte Damage under Oxidative Stress

Inhibitors of human poly(ADP-ribose) polymerase (PARP) are considered as promising agents for treatment of cardiovascular, neurological, and other diseases accompanied by inflammation and oxidative stress. Previously, the ability of natural compounds 7-methylguanine (7mGua) and 8-hydroxy-7-methylguanine (8h7mGua) to suppress activity of the recombinant PARP protein was demonstrated. In the present work, we have investigated the possibility of PARP-inhibitory and cytoprotective action of 7mGua and 8h7mGua against the rat cardiomyoblast cultures (undifferentiated and differentiated H9c2). It was found that 7mGua and 8h7mGua rapidly penetrate into the cells and effectively suppress the H2O2-stimulated PARP activation (IC50 = 270 and 55 μM, respectively). The pronounced cytoprotective effects of 7mGua and 8h7mGua were shown in a cellular model of oxidative stress, and effectiveness of 8h7mGua exceeded the classic PARP inhibitor 3-aminobenzamide. The obtained data indicate promise for the development of PARP inhibitors based on guanine derivatives and their testing using the models of ischemia-reperfusion tissue damage.

 

Comments:

This sounds like a fascinating study! It's intriguing how 7-methylguanine (7mGua) and 8-hydroxy-7-methylguanine (8h7mGua) exhibit potential as inhibitors of poly(ADP-ribose) polymerase (PARP), especially in the context of treating conditions associated with inflammation and oxidative stress.

The ability of these compounds to effectively penetrate cells and suppress H2O2-stimulated PARP activation is a significant finding. Additionally, demonstrating their cytoprotective effects against oxidative stress in rat cardiomyoblast cultures, surpassing the effectiveness of a classic PARP inhibitor like 3-aminobenzamide, is quite promising.

Utilizing guanine derivatives as a foundation for PARP inhibitors opens doors for further exploration in developing therapeutic agents. Testing these inhibitors in models of ischemia-reperfusion tissue damage could provide valuable insights into their potential clinical applications for conditions related to such damage.

It's impressive how these natural compounds show such potential. What's particularly exciting is their ability to rival or even surpass the effectiveness of established synthetic PARP inhibitors. This could pave the way for novel treatments for various diseases where inflammation and oxidative stress play crucial roles.

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Cat.No. Product Name Information
S1132 3-Aminobenzamide 3-Aminobenzamide (3-ABA , 3-Amino Benzamide, 3-AB) is a potent inhibitor of Poly(ADP-ribose)polymerase (PARP) and inhibits cell apoptosis after SCI (Spinal Cord Injury) in caspase-independent way.

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Apoptosis related