Efficient one-pot synthesis of arylated pyrazole-fused pyran analogs: as leads to treating diabetes and Alzheimer’s disease - SUPPLEMENTARY MATERIAL

  

Table S1: In vitro α-amylase, α-glucosidase, AChE and BChE inhibitory activity of arylated pyrazole fused pyran analogs 1-20

  

Table S2: Kinetic studies of active compounds for α-amylase and α-glucosidase inhibition

  

Fig. S1: Kinetic studies of α-amylase inhibition (A) Lineweaver-Burk plot of 1/[S] vs 1/Rate in the different concentrations of competitive type inhibitors. (B) Hill plot of different concentrations of [S] vs Rate (Vmax-Rate) in the different concentrations of competitive type inhibitor. (C) Hanes-Woolf plot of compound 7 at different concentrations of [S] vs [S]/Rate in the different concentrations of competitive type inhibitor. (D) Eadie-Hofstee plot of compound 7 by rate/[S] vs Rate in the different concentrations of competitive type inhibitor. (E) Dixon plot of compound 7 at different concentrations of competitive inhibitor vs 1/Rate. (F) The scattered plot of compound 7 by Rate vs Rate/[S] in the different concentrations of competitive type inhibitors.

  

Fig. S2: Kinetic studies of α-glucosidase inhibition (A) Lineweaver-Burk plot of 1/[S] Vs 1/Rate in the different concentrations of non-competitive type inhibitor. (B) Hill plot of different concentrations of [S] vs Rate (Vmax-Rate) in the different concentrations of non-competitive type inhibitor. (C) Hanes-Woolf plot of compound 7 at different concentrations of [S] vs [S]/Rate in the different concentrations of non-competitive type inhibitor. (D) Eadie-Hofstee plot of compound 7 by rate/[S] vs Rate in the different concentrations of non-competitive type inhibitor. (E) Dixon plot of compound 7 at different concentrations of non-competitive inhibitor vs 1/Rate. (F) The scattered plot of compound 7 by Rate vs Rate/[S] in the different concentrations of non-competitive type inhibitor.

Table S3: Kinetic studies of active compounds for AChE and BChE inhibitory activities

  

Fig. S3: Kinetic studies of AChE inhibition (A) Lineweaver-Burk plot of 1/[S] vs 1/Rate in the different concentrations of competitive type inhibitors. (B) Hill plot of different concentrations of [S] vs Rate (Vmax-Rate) in the different concentrations of competitive type inhibitor. (C) Hanes-Woolf plot of compound 7 at different concentrations of [S] vs [S]/Rate in the different concentrations of competitive type inhibitor. (D) Eadie-Hofstee plot of compound 7 by rate/[S] vs Rate in the different concentrations of competitive type inhibitor. (E) Dixon plot of compound 7 at different concentrations of competitive inhibitor vs 1/Rate. (F) The scattered plot of compound 7 by Rate vs Rate/[S] in the different concentrations of competitive type inhibitors.

  

Fig. S4: Kinetic studies of BChE inhibition (A) Lineweaver-Burk plot of 1/[S] vs 1/Rate in the different concentrations of competitive type inhibitors. (B) Hill plot of different concentrations of [S] vs Rate (Vmax-Rate) in the different concentrations of competitive type inhibitor. (C) Hanes-Woolf plot of compound 7 at different concentrations of [S] vs [S]/Rate in the different concentrations of competitive type inhibitor. (D) Eadie-Hofstee plot of compound 7 by rate/[S] vs Rate in the different concentrations of competitive type inhibitor. (E) Dixon plot of compound 7 at different concentrations of competitive inhibitor vs 1/Rate. (F) The scattered plot of compound 7 by Rate vs Rate/[S] in the different concentrations of competitive type inhibitors.

  

Fig. S5: Comparison of DPPH and ABTS activities of compounds 1-20

  

Fig. S6: The correlation plot between IC50 and docking scores (S) (α-amylase enzyme). The molecular docking shows a good correlation with the experimental values. The value of a correlation coefficient is 0.2929

Table S4: The interactions of the compounds with the active site of the α-amylase enzyme

 Fig. S7: (A) 3D interaction diagram of compound 4 (blue), (B) compound 2 (yellow), (C) compound 7 (orange), (D) compound 20 (purple), (E) compound 11 (magenta), and (F) control acarbose (green) showing interactions with the active site of the α-glucosidase enzyme. 

  

Fig. S8: A correlation graph for IC50 values vs predicted docking score (S) (α-glucosidase enzyme). The docking scores of all the compounds were showing a correlation with the experimental results with a correlation coefficient of R = 0.0852

Table S5: The interactions of the compounds with the active site of the α-glucosidase enzyme

  

Table S6: The docking scores and interactions of the compounds with the active site of the acetylcholinesterase enzyme

  

Fig. S9: (A) The 3D interaction diagram of compound 4 (yellow), (B) compound 7 (pink), (C) compound 2 (orange), (D) compound 20 (green), (E) compound 11 (purple), and (F) control donepezil (yellow) showing interactions with the active site of the AChE enzyme.

  

Fig. S10: A correlation graph for IC50 values vs predicted docking score (S) AChE enzyme. The value of the correlation coefficient is 0.4016

  

Fig. S11: (A) The interactions of compound 4 (salmon), (B) compound 7 (aquamarine), (C) compound 2 (hot pink), (D) compound 20 (green), (E) Compound 11 (blue), and (F) control donepezil (yellow)displays interactions with active site residues of BChE enzyme

  

Fig. S12: A correlation graph for IC50 values vs predicted docking score (S) BChE enzyme. The value of the correlation coefficient is 0.497

Table S7: The docking scores and interactions of the compounds with the active site of the butyrylcholinesterase enzyme