Table 1.
The list of different classes of synthetic compounds used in this study.
Fig 1.
(a) Graph representing IC50 value of compound 25 calculated through non-linear regression analysis, (b) Line-weaver Burk plot for compound 25 representing an un-competitive type of enzyme inhibition, (c) Graph representing IC50 value of compound 228 (d) Line-weaver Burk plot for compound 228 representing an un-competitive type of enzyme inhibition by using GraphPad Prism 7.04.
Table 2.
IC50 values of the most active compounds against α-glucosidase.
Fig 2.
2D, ball and stick model docking pose of compound 25 (a), compound 228 (b), compound 212 (d), and co-crystallized ligand (c). The yellow ball represents carbon atoms, red represents oxygen, blue represents nitrogen, green represents chlorine, brown represents sulfur and cyan represents fluorine. Amino acid residues are shown in the disc model with different colors depending on type of interaction. Green colored disc with dotted lines represents conventional hydrogen bond, dark purple discs represent pi-pi T-shaped interaction, light purple represents pi-alkyl interaction, blue disc with dotted lines represents halogen bond and light blue represents carbon-hydrogen (c) or pi-donor hydrogen (d) bond.Molecular docking studies indicated that compound 25 interacts with Lys414, Arg466, and His540 through conventional hydrogen bond, Phe277 through pi-pi T-shaped, Asp306 through halogen bond, and Trp479 and Phe515 through pi-alkyl interaction as given in Fig 2A. Compound 228 interacts with Asp185, 306, 416, and 482, Arg420 and 466, Lys414, and His54 through conventional hydrogen bonds, Phe277 through pi-pi T-shaped, and Phe417 and Trp380 through pi-alkyl interactions as shown in Fig 2B. Re-docking of co-crystallized ligand indicated conventional hydrogen bonds with Asp306 and 482, Cys307, Trp345, Lys414, Arg466, and His540 as given in Fig 2C. Compound 212 makes conventional hydrogen bonds with Asp184 and Arg420, pi-pi T-shaped with Phe277 and 417, and other pi-alkyl interactions as shown in Fig 2D. According to molecular docking studies, the most active compounds, 25 and 228 have almost similar interactions as compared to the co-crystallized ligand however, compound 212 have slightly different interactions. Structure-activity relationship (SAR), suggests that the activity of the compounds depends on cyclohexane/benzene ring (6-C) with -OH and/or Halogen substitution.