Comparative study of the antioxidant properties of monocarbonyl curcumin analogues C66 and B2BrBC in isoproteranol induced cardiac damage

Abstract

Aim: To test the antioxidant properties of the newly synthesized (2E,6E)-2,6-bis(2-bromobenzylidene)cyclohexanone (B2BrBC) in parallel with C66 in rats with cardiac hypertrophy.

Materials and methods: The protective effects of both C66 and B2BrBC against oxidative stress in rats with cardiac hypertrophy, was studied by evaluating the activity of antioxidant enzymes, the relationship between the ratio of the activities of the antioxidant enzymes R = SOD/(GPx + CAT) and levels of thiols and lipid peroxidation in the heart. In order to gain better understanding of the antioxidant properties of the studied compounds, computational methods were utilized. The properties of selected structurally related derivatives were obtained on optimized geometries for ground states, using semi-empirical PM3 quantum mechanical calculations.

Key findings: The ratio R shows disequilibrium in rats with induced hypertrophy (p < 0.001). Coextending changes were detected in total and free sulfhydryl group content (p = 0.011 for t-SH and p = 0.008, for free SH, respectively). The results with the B2BrBC, indicated strong thiol prevention reflected in the levels of both t-SH and f-SH. Taking into account the HOMO energies of B2BrBC (-9.398 eV) and C66 (-9.667), it can be concluded that B2BrBC has lower HOMO energy, which makes it a better electron donor and a better antioxidant.

Significance: The obtained results indicated that the antioxidant ability of B2BrBC is positively associated with the catalytic SOD and GPx activities expressed through preserved t-SH levels. It seems plausible that for a compound to exhibit antioxidant activity, as most of the 2,6-bis(benzylidene)cyclohexanones do, they should be good electron donors.

Impact statement: Understanding the relationship between cardiac hypertrophy induced oxidative injuries and supporters of endogenous reparatory machinery will help in establishing the beneficial role of adequate antioxidant supplementation. In this study reliable data on the preventive effects of newly synthesized symmetric monocarbonyl curcumin analogue B2BrBC and its role in the prevention of oxidative injuries on three levels (enzymatic, protein and lipid), in the heart hypertrophic onset, were obtained.

Keywords: (2E,6E)-2,6-bis(2-bromobenzylidene)cyclohexanone; Antioxidant enzymes; Cardiac hypertrophy; Heart; Malondialdehyde; Sulfhydryl groups.