Inhibitory effects of selected antibiotics on the activities of α-amylase and α-glucosidase: In-vitro, in-vivo and theoretical studies.

Antibiotics are effective drugs that are used to treat infectious diseases either by killing bacteria or slowing down their growth. The well-adapted structural features of antibiotics for the inhibition/activation of enzymes include several available hydrogen bond (H-bond) acceptors and donors, flexible backbone and hydrophobic nature. The substrates of α-amylase and α-glucosidase, known as key absorbing enzymes, have functional groups (OH groups) rembling antibiotics. Given the possibility of developing in diabetics and the significant association between diabetes and infection, the present study was conducted to investigate the influences of tetracycline (TET), kanamycin (KANA), lincomycin (LIN), erythromycin (ERM) and azithromycin (AZM) on α-glucosidase and α-amylase activities with calculating IC50 and Ki values. Also, the efficacy of antibiotics after oral administration was evaluated by analysis of blood glucose concentrations in rats, as well as a molecular docking analysis was explored. α-glucosidase and α-amylase activities were inhibited in a dose dependent fashion by TET with an IC50 of 38.7 ± 1.4 and 47.8 ± 3.2 μM respectively, by KANA with an IC50 of 46.2 ± 1.6 and 65.1 ± 1.6, by LIN with an IC50 of 59.1 ± 2.1 and 51.3 ± 4.1, by ERM with an IC50 of 94.9 ± 4.7 and 65.7 ± 3.8 and by AZM with an IC50 of 69.4 ± 4.4 and 103.6 ± 6.2. Moreover, the Ki values of TET were calculated as 4.4 ± 0.6 and 8.4 ± 0.8 μM for α-glucosidase and α-amylase in a competitive-mode and mixed-mode inhibition. In addition, to communicate with the active site of α-glucosidase and α-amylase respectively, TET presented a binding energy of -9.8 and -8.8 kcal/mol, KANA -7.9 and -7.1, LIN -7.8 and -6.7, ERM -6.8 and -6.4, and AZM -6.4 and -7.5 kcal/mol. In-vivo studies also suggested a decrease in the blood glucose concentration after administering TET compared to the positive controls (P < 0.01). The results obtained from the present research can therefore help the scientific community explore the possible interconnection between the clinical side-effects of antibiotics and their α-glucosidase and α-amylase inhibitory properties, as the target enzymes in hypoglycemia conditions.