A novel synthetised sulphonylhydrazone coumarin (E)-4-methyl-N'-(1-(3-oxo-3H-benzo[f]chromen-2- yl)ethylidene)benzenesulphonohydrazide protect against isoproterenol-induced myocardial infarction in rats by attenuating oxidative damage, biological changes and electrocardiogram.

Coumarins and their derivatives are becoming a potential source for new drug discovery due to their vast array of biological activities. The present study was designed to investigate the cardioprotective effects of a newly synthesised coumarin, symbolised as 5,6-PhSHC, against cardiac remodelling process in isoproterenol (ISO) induced myocardial infarction (MI) in male Wistar rats by evaluating haematological, biochemical and cardiac biomarkers. Rats were pre/co-treated with 5,6-PhSHC or clopidogrel (150 µg/kg body weight) daily for a period of 7 days and then MI was induced by injecting ISO (85 mg/kg body weight), at an interval of 24 hours for 2 consecutive days, on the sixth and seventh days. The in vivo exploration indicated that the injection of 5,6-PhSHC improved the electrocardiographic (ECG) pattern and prevented severe heart damage by reducing leakage of the cardiac injury markers, such as troponin-T (cTn-T), lactate dehydrogenase (LDH), and creatine kinase-MB. The cellular architecture of cardiac sections, altered in the myocardium of infracted rats, was reversed by 5,6-PhSHC treatment. Results showed that injection of 5,6-PhSHC elicited significant cardioprotective effects by prevention of myocardium cell necrosis and inflammatory cells infiltration, along with marked decrease in plasma levels of fibrinogen. In addition, the total cholesterol, triglyceride, LDL-c, and HDL profiles underwent remarkable beneficial changes. It was also interesting to note that 5,6-PhSHC enhanced the antioxidative defence mechanisms by increasing myocardial glutathione (GSH) level, superoxide dismutase (SOD), and catalase (CAT) activities, together with reducing the levels of thiobarbituric-acid-reactive substances (TBARS), when compared with ISO-induced rats. Taken together, these findings suggested a beneficial role for 5,6-PhSHC against ISO-induced MI in rats. Furthermore, in silico analysis showed that 5,6-PhSHC possess high computational affinities (E-value >-9.0 kcal/mol) against cyclooxygenase-2 (PDB-ID: 1CX2), vitamin K epoxide reductase (PDB-ID: 3KP9), glycoprotein-IIb/IIIa (PDB-ID: 2VDM) and catalase (PDB-ID: 1DGF). Therefore, the present study provided promising data that the newly synthesised coumarin can be useful in the design and synthesis of novel drug against myocardial infarction.

(E)-N'-(1-(7-Hydroxy-2-Oxo-2H-Chromen-3-Yl) Ethylidene) Benzohydrazide, a Novel Synthesized Coumarin, Ameliorates Isoproterenol-Induced Myocardial Infarction in Rats through Attenuating Oxidative Stress, Inflammation, and Apoptosis.

The present study was directed to investigate the effect of precotreatment with (E)-N'-(1-(7-hydroxy-2-oxo-2H-chromen-3-yl) ethylidene) benzohydrazide (7-hyd.HC), a novel potent synthesized coumarin, on isoproterenol- (ISO-) induced myocardial infarction (MI) in rats. The hydrazone compound was characterized by IR, 1D, and 2D NMR analyses. Experimental induction of MI in rats was established by ISO (85 mg/kg/day, s.c) for two consecutive days (6th and 7th days). 7-hyd.HC or sintrom was given for 7 days prior and simultaneous to ISO injection. 7-hyd.HC offered a cardiopreventive effect by preventing heart injury marker leakage (LDH, ALT, AST, CK-MB, and cTn-I) from cardiomyocytes and normalizing cardiac function and ECG pattern, as well as improving lipid profile (TC, TG, LDL-C, and HDL-C), which were altered by ISO administration. Moreover, 7-hyd.HC precotreatment significantly mitigated the oxidative stress biomarkers, as evidenced by the decrease of lipid peroxidation and the increased level of the myocardial GSH level together with the SOD, GSH-Px, and catalase activities. 7-hyd.HC inhibited the cardiac apoptosis by upregulating the expression of Bcl-2 and downregulating the expression of Bax and caspase-3 genes. In addition, 7-hyd.HC reduced the elevated fibrinogen rate and better prevented the myocardial necrosis and improved the interstitial edema and neutrophil infiltration than sintrom. Overall, 7-hyd.HC ameliorated the severity of ISO-induced myocardial infarction through improving the oxidative status, attenuating apoptosis, and reducing fibrinogen production. The 7-hyd.HC actions could be mediated by its antioxidant, antiapoptotic, and anti-inflammatory capacities.

Cardioprotective effects of (E)-4-hydroxy-N'-(1-(3-oxo-3H-benzo[f]chromen-2-yl)ethylidene)benzohydrazide: a newly synthesized coumarin hydrazone against isoproterenol-induced myocardial infarction in a rat model.

The current study was carried out to evaluate the effect of pretreatment and co-treatment with a newly synthesized coumarin hydrazone, (E)-4-hydroxy-N'-(1-(3-oxo-3H-benzo[f]chromen-2-yl)ethylidene)benzohydrazide (hereinafter EK6), against isoproterenol-induced myocardial infarction in rats. Changes in biochemistry, cardiac biomarkers, electrocardiography, and histopathology after treatment with EK6 or acenocoumarol (Sintrom) were studied. Animals were randomly divided into 4 groups: vehicle control (C), isoproterenol + Sintrom (ISO + Sin), isoproterenol + EK6 (ISO + EK6), and isoproterenol (ISO). Myocardial infarction was induced by subcutaneous ISO administration at a dose of 85 mg·kg-1·day-1 with a drug-free interval of 24 h on days 6 and 7. Treatment with ISO led to significant elevation (p < 0.05) in serum levels of cardiac injury biomarkers, namely cardiac troponin-T, lactate dehydrogenase, creatine kinase-MB, alanine aminotransferase, and aspartate aminotransferase compared with levels in the vehicle control. A change in the lipid profile was also observed as a significant increase in total cholesterol and triglycerides. Furthermore, ISO caused significant alterations in the electrocardiogram pattern, including significant ST-segment elevation, significant decreased R wave amplitude, and significant increase in heart rate (16%) as well as marked changes in the histopathology of the heart tissue. Pretreatment and co-treatment with newly synthesized coumarin hydrazone restored all ISO-induced biochemical, lipid, cardiac, and histopathological changes in rats with myocardial infarction.

Contribution of adiponectin polymorphisms to the risk of coronary artery disease in a North-African Tunisian population.

BACKGROUND: Adiponectin, an adipocyte-derived protein, is known to play a key role in the processes leading to atherosclerosis and coronary artery disease (CAD) through its anti-atherogenic, anti-inflammatory, antioxidative, and anti-apoptotic properties. In the current study, we have studied the association of two single nucleotide polymorphisms (SNPs) +45 T>G (rs2241766) and +276 G>T (rs1501299) of the adiponectin gene with coronary artery disease (CAD) on an Arab/North-African population from Tunisia. METHODS: Subjects comprised 277 patients with angiographically demonstrated CAD and 269 age- and gender-matched control subjects. The adiponectin genotypes were performed by polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP). The contribution of adiponectin variants to CAD was analyzed by haplotype and regression analysis. RESULTS: Adiponectin +45T>G and +276G>T genotypic and allelic distributions did not show a significant difference between cases and controls. Similarly, no association with CAD was observed for the haplotype analysis. Assuming dominant model of transmission for both polymorphisms and after adjustment of a number of traditional risk factors for CAD, logistic regression analysis showed an association of SNP +45 T>G with increased risk of developing CAD [adjusted OR (95% CI) = 2.59 (1.17-5.70); P = .01]. However, SNP + 276 G>T is associated with decreased risk of developing CAD [adjusted OR (95% CI) = 0.47 (0.22-0.97); P = .04]. CONCLUSION: There is no allelic or genotypic association of +45 T>G and +276 G>T of the adiponectin gene with CAD in the Tunisian population.