Abstract
In the present study, twenty (20) structural variants of nitrofurazone were synthesized based on BIODS (Biology-oriented drug synthesis) approach. The structure elucidation of the synthetic molecules (1–20) was carried out using different spectroscopic techniques, and their α-glucosidase inhibitory activity was also determined. The synthetic molecules 1–20 exhibited good α-glucosidase inhibition than the parent, nitrofurazone. Four compounds 2, 4, 6, and 7 showed potential inhibition against α-glucosidase with IC50 values ranging between 0.63 ± 0.25–1.29 ± 0.46 µM as compared to the standard acarbose (IC50 = 2.05 ± 0.41 µM). Nevertheless, compounds 15 (IC50 = 0.74 ± 0.12 µM), and 19 (IC50 = 0.54 ± 0.3 µM) also displayed good α-glucosidase inhibition and compound 19 was the most active compound of the series. Kinetic study of the active compounds 7 and 19 was also carried out to confirm the mode of inhibition. The binding interactions of the most active compounds within the active site of enzyme were determined by molecular docking. Moreover, molecular dynamic simulation of compound 19 was also performed in order to determine the stability of the overall complex (α-glucosidase + c19) in an explicit watery environment. The synthetic molecules were predicted as non-cytotoxic, however, seven compounds 1, 3, 4, 9, 10, 11, and 12 were predicted as carcinogenic.