Potential effect of new (E)-4-hydroxy -N'-(1-(7-hydroxy-2-oxo-2H-chromen-3-yl) ethylidene) benzohydrazide against acute myocardial infarction: Hemodynamic, biochemical and histological studies

This study aimed to explore the cardioprotective effect of new synthesized coumarin (E)-4-hydroxy-N'-(1-(7-hydroxy-2-oxo-2H-chromen-3-yl) ethylidene) benzohydrazide denoted (Hyd.Cou) against myocardial infarction disorders. Male Wistar rats were divided into four groups; Control, ISO, ISO+ Ac (Acenocoumarol) and ISO+ Hyd.Cou. Results showed that ISO group exhibited serious alteration in EGC pattern, significant heart hypertrophy (+33%), hemodynamic disturbance and increase in plasma rate of CK-MB, LDH and troponin-T by 44, 53, and 170%, respectively, as compared to Control. Moreover, isoproterenol induced a rise in plasma angiotensin-converting enzyme activity (ACE) by 49%, dyslipidemia, and increased Thiobarbituric acid-reactive substances (TBARS) by 117% associated with decrease in the activity of superoxide dismutase (SOD) and glutathione peroxidase (GPx) by 46% and 58%, respectively in myocardium. Interestingly, the molecular docking calculation demonstrated strong interactions of Hyd.Cou with the receptors of the protein disulfide isomerase (PDI) which could highlight the antithrombotic effect. Moreover, Hyd.Cou improved plasma cardiac dysfunction biomarkers, mitigated the ventricle remodeling process and alleviated heart oxidative stress damage. Overall, Hyd.Cou prevented the heart from remodeling process through inhibition of ACE activity and oxidative stress improvement.

Keywords: Coumarin; Molecular docking; Myocardial infarction; Oxidative stress; Protein disulfide isomerase; dyslipidemia.