DOI: 10.25402/fmc.21378210.v1
title: Efficient one-pot synthesis of arylated pyrazole-fused pyran analogs: as leads to treating diabetes and Alzheimer’s disease - SUPPLEMENTARY MATERIAL

description:   
<strong>Table S1:</strong> <em>In vitro</em> <em>α</em>-amylase, <em>α</em>-glucosidase, AChE and BChE inhibitory activity of arylated pyrazole fused pyran analogs <strong>1-20</strong>
  
<strong>Table S2:</strong> <strong>Kinetic studies of active compounds for </strong><em><strong>α</strong></em><strong>-amylase and </strong><em><strong>α</strong></em><strong>-glucosidase</strong> <strong>inhibition</strong>
  
<strong>Fig. S1:</strong> Kinetic studies of <em>α</em>-amylase inhibition <strong>(A)</strong> Lineweaver-Burk plot of 1/[S] vs 1/Rate in the different concentrations of competitive type inhibitors. <strong>(B)</strong> Hill plot of different concentrations of [S] vs Rate (Vmax-Rate) in the different concentrations of competitive type inhibitor. <strong>(C)</strong> Hanes-Woolf plot of compound <strong>7 </strong>at different concentrations of [S] vs [S]/Rate in the different concentrations of competitive type inhibitor. <strong>(D)</strong> Eadie-Hofstee plot of compound <strong>7</strong> by rate/[S] vs Rate in the different concentrations of competitive type inhibitor. <strong>(E)</strong> Dixon plot of compound <strong>7</strong> at different concentrations of competitive inhibitor vs 1/Rate. <strong>(F)</strong> The scattered plot of compound <strong>7</strong> by Rate vs Rate/[S] in the different concentrations of competitive type inhibitors.
  
<strong>Fig. S2:</strong> Kinetic studies of <em>α</em>-glucosidase inhibition <strong>(A)</strong> Lineweaver-Burk plot of 1/[S] Vs 1/Rate in the different concentrations of non-competitive type inhibitor. <strong>(B)</strong> Hill plot of different concentrations of [S] vs Rate (Vmax-Rate) in the different concentrations of non-competitive type inhibitor. <strong>(C)</strong> Hanes-Woolf plot of compound <strong>7</strong> at different concentrations of [S] vs [S]/Rate in the different concentrations of non-competitive type inhibitor. <strong>(D)</strong> Eadie-Hofstee plot of compound <strong>7</strong> by rate/[S] vs Rate in the different concentrations of non-competitive type inhibitor. <strong>(E)</strong> Dixon plot of compound <strong>7</strong> at different concentrations of non-competitive inhibitor vs 1/Rate. <strong>(F)</strong> The scattered plot of compound <strong>7</strong> by Rate vs Rate/[S] in the different concentrations of non-competitive type inhibitor.
<strong>Table S3: Kinetic studies of active compounds for AChE and BChE inhibitory activities</strong>
  
<strong>Fig. S3:</strong> Kinetic studies of AChE inhibition <strong>(A)</strong> Lineweaver-Burk plot of 1/[S] vs 1/Rate in the different concentrations of competitive type inhibitors. <strong>(B)</strong> Hill plot of different concentrations of [S] vs Rate (Vmax-Rate) in the different concentrations of competitive type inhibitor. <strong>(C)</strong> Hanes-Woolf plot of compound <strong>7</strong> at different concentrations of [S] vs [S]/Rate in the different concentrations of competitive type inhibitor. <strong>(D)</strong> Eadie-Hofstee plot of compound <strong>7</strong> by rate/[S] vs Rate in the different concentrations of competitive type inhibitor. <strong>(E)</strong> Dixon plot of compound <strong>7</strong> at different concentrations of competitive inhibitor vs 1/Rate. <strong>(F)</strong> The scattered plot of compound <strong>7</strong> by Rate vs Rate/[S] in the different concentrations of competitive type inhibitors.
  
<strong>Fig. S4:</strong> Kinetic studies of BChE inhibition <strong>(A)</strong> Lineweaver-Burk plot of 1/[S] vs 1/Rate in the different concentrations of competitive type inhibitors. <strong>(B)</strong> Hill plot of different concentrations of [S] vs Rate (Vmax-Rate) in the different concentrations of competitive type inhibitor. <strong>(C)</strong> Hanes-Woolf plot of compound <strong>7</strong> at different concentrations of [S] vs [S]/Rate in the different concentrations of competitive type inhibitor. <strong>(D)</strong> Eadie-Hofstee plot of compound <strong>7</strong> by rate/[S] vs Rate in the different concentrations of competitive type inhibitor. <strong>(E)</strong> Dixon plot of compound <strong>7</strong> at different concentrations of competitive inhibitor vs 1/Rate. <strong>(F)</strong> The scattered plot of compound <strong>7</strong> by Rate vs Rate/[S] in the different concentrations of competitive type inhibitors.
  
<strong>Fig. S5:</strong> Comparison of DPPH and ABTS activities of compounds <strong>1-20</strong>
  
<strong>Fig. S6:</strong> The correlation plot between IC50 and docking scores (S) (<em>α</em>-amylase enzyme). The molecular docking shows a good correlation with the experimental values. The value of a correlation coefficient is 0.2929
<strong>Table S4:</strong> The interactions of the compounds with the active site of the <em>α</em>-amylase enzyme
 <strong>Fig. S7:</strong> <strong>(A)</strong> 3D interaction diagram of compound <strong>4</strong> (blue), <strong>(B)</strong> compound <strong>2</strong> (yellow), <strong>(C)</strong> compound <strong>7</strong> (orange), <strong>(D)</strong> compound <strong>20</strong> (purple), <strong>(E)</strong> compound <strong>11</strong> (magenta), and <strong>(F)</strong> control acarbose (green) showing interactions with the active site of the <em>α-</em>glucosidase enzyme. 
  
<strong>Fig. S8:</strong> A correlation graph for IC50 values <em>vs</em> predicted docking score (S) (<em>α</em>-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
<strong>Table S5:</strong> The interactions of the compounds with the active site of the <em>α</em>-glucosidase enzyme
  
<strong>Table S6:</strong> The docking scores and interactions of the compounds with the active site of the acetylcholinesterase enzyme
  
<strong>Fig. S9:</strong> <strong>(A)</strong> The 3D interaction diagram of compound <strong>4</strong> (yellow), <strong>(B)</strong> compound <strong>7</strong> (pink), <strong>(C)</strong> compound <strong>2</strong> (orange), <strong>(D)</strong> compound <strong>20</strong> (green), <strong>(E)</strong> compound <strong>11</strong> (purple), and <strong>(F)</strong> control donepezil (yellow) showing interactions with the active site of the AChE enzyme.
  
<strong>Fig. S10:</strong> A correlation graph for IC50 values <em>vs</em> predicted docking score (S) AChE enzyme. The value of the correlation coefficient is 0.4016
  
<strong>Fig. S11:</strong> <strong>(A)</strong> The interactions of compound <strong>4</strong> (salmon), <strong>(B)</strong> compound <strong>7</strong> (aquamarine), <strong>(C)</strong> compound <strong>2</strong> (hot pink), <strong>(D)</strong> compound <strong>20</strong> (green), <strong>(E)</strong> Compound <strong>11</strong> (blue), and <strong>(F)</strong> control donepezil (yellow)displays interactions with active site residues of BChE enzyme
  
<strong>Fig. S12: </strong>A correlation graph for IC50 values <em>vs</em> predicted docking score (S) BChE enzyme. The value of the correlation coefficient is 0.497
<strong>Table S7:</strong> The docking scores and interactions of the compounds with the active site of the butyrylcholinesterase enzyme
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