A novel ferulic acid derivative attenuates myocardial cell hypoxia reoxygenation injury through a succinate dehydrogenase dependent antioxidant mechanism.

The molecular structure optimization aimed at definite target is expected to improve its anti-myocardial ischemia reperfusion (I/R) injury. Ferulic acid derivatives could probably attenuate myocardial I/R injury when optimized on account of definite target succinate dehydrogenase (SDH). Herein, an original compound hmy-paa (3-(4-hydroxy-3-methoxyphenyl)-N-(1H-pyrazol-3-yl)acrylamide), a combination of ferulic acid and active groups of enzyme inhibitor was synthesized, myocardial cell hypoxia reoxygenation (H/R) model were built, and SDH activity of myocardial cell was detected to investigate the effect of the derivative. Intriguingly, it could selectively inhibit SDH activity, and efficiently abate myocardial cell H/R injury. SDH is located in the mitochondrial inner membrane, and fluorescent hmy-paa could be observed to accumulate in cell and mitochondria through fluorescence inversion microscopy, which allows for more efficient SDH inhibition efficacy. By inhibiting SDH activity, hmy-paa could reduce oxidative damage by preventing excess production of intracellular reactive oxygen species as well as ensure energy production through the regulation of ATP level. The computational docking simulation exhibits a tightly bound mode between hmy-paa and SDH. Consequently, ferulic acid derivative hmy-paa is a new candidate for the treatment of myocardial H/R injury that exerts its therapeutic effect through a SDH dependent antioxidant mechanism. SDH could probably be a new target for drug discovery to alleviate myocardial I/R injury.