Antioxidant and antidiabetic potentials of methoxy-substituted Schiff bases using in vitro, in vivo, and molecular simulation approaches

The current study attempted to synthesize methoxy-substituted Schiff’s bases, namely MK1 and MK2, and evaluate their antidiabetic effects using , , and molecular docking studies. Experimental animals (rat model) received the synthetic compounds, MK1 and MK2, orally in doses of 25 and 50 mg/kg body weight, respectively. When comparing compound MK2 at the tested doses to glibenclamide on day 28, the diabetic rats’ blood glucose levels were nearly normal (139.02 and 121.23 mg/dL at 25 and 50 mg/kg body weight doses). The IC for MK1 against α-glucosidase inhibitory potential was found to be 281.29 μg/mL, while for MK2, it is reported to be 204.69 μg/mL. Furthermore, the acute toxicity, lipid profile, and its effect on blood biochemical parameters were also examined. In addition, through analysis, the binding of MK1 and MK2 was elucidated with α-glucosidase enzyme, showcasing its antidiabetic mechanism at molecular levels. The studies also predicted the two compounds to be inactive toward the human hERGs cardiac potassium channel, which indicates no potential risk of cardiac toxicity. Overall, the toxicity predictions suggest that compounds MK1 and MK2 are non-toxic and non-carcinogenic.