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Scheme 1.

Already reported aldo-keto reductase inhibitors [14, 15].

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Scheme 1 Expand

Fig 1.

Optimized structures of quinolone derivatives.

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Fig 1 Expand

Table 1.

Calculation of energetic parameters and quantum chemical descriptors of quinolone derivatives.

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Table 1 Expand

Fig 2.

HOMO and LUMO structures of quinolone derivatives in gas and solvent (water) phase.

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Fig 2 Expand

Table 2.

Quantum chemical descriptors of quinolone derivatives in gas phase.

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Table 2 Expand

Fig 3.

Molecular electrostatic potential (MEP) structures of quinolone derivatives in gas phase and solvent phase as well.

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Fig 3 Expand

Fig 4.

3D and 2D interactions of Nap (co-crystal ligand) with active site of AKR1B1.

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Fig 4 Expand

Table 3.

Binding energies of quinolone derivatives with target AKR1B1 and AKR1B10 (kJ/mol).

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Table 3 Expand

Fig 5.

3D and 2D interactions of quinidine with active site of AKR1B1.

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Fig 5 Expand

Fig 6.

3D and 2D interactions of quinine with active site of AKR1B1.

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Fig 6 Expand

Fig 7.

3D and 2D interactions of Nap (co-crystal ligand) with active site of AKR1B10.

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Fig 7 Expand

Fig 8.

3D and 2D interactions of quinidine with active site of AKR1B10.

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Fig 8 Expand

Fig 9.

3D and 2D interactions of quinine with active site of AKR1B10.

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Fig 9 Expand

Fig 10.

3D and 2D interactions of quinine with active site of nuclear factor kappa B (NF-κB).

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Fig 10 Expand

Fig 11.

3D and 2D interactions of quinidine with active site of nuclear factor kappa B (NF-κB).

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Fig 11 Expand

Fig 12.

. 3D and 2D interactions of quinidine with active site of cellular tumor antigen P53.

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Fig 12 Expand

Fig 13.

3D and 2D interactions of quinine with active site of cellular tumor antigen P53.

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Fig 13 Expand

Fig 14.

3D and 2D interactions of quinine with active site of caspase-3.

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Fig 14 Expand

Fig 15.

3D and 2D interactions of quinidine with active site of caspase-3.

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Fig 15 Expand

Fig 16.

Root mean square deviation (RMSD) of the C-alpha atoms of AKR1B1-Quinine, AKR1B1-Quinidine; AKR1B10-Quinine, AKR1B10-Quinidine complexes with time.

The left Y-axis shows the variation of protein RMSD through time. The right Y-axis shows the variation of ligand RMSD through time.

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Fig 16 Expand

Fig 17.

Residue wise Root Mean Square Fluctuation (RMSF) of the C-alpha atoms of AKR1B1-Quinine, Quinidine; AKR1B10-Quinine, Quinidine complexes with time.

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Fig 17 Expand

Fig 18.

AKR1B1, AKR1B10 bound with quinidine secondary structure element distribution by residue index.

The colours red and blue represent alpha helices and beta strands, respectively.

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Fig 18 Expand

Fig 19.

AKR1B1, AKR1B10 bound with quinine secondary structure element distribution by residue index.

The colours red and blue represent alpha helices and beta strands, respectively.

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Fig 19 Expand

Table 4.

Physicochemical properties of quinolone derivatives.

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Table 4 Expand

Table 5.

ADMET properties of the quinolone derivatives.

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Table 5 Expand