Investigation of inhibition of human glucose 6-phosphate dehydrogenase by some 99mTc chelators by in silico and in vitro methods

Figures & data

Figure 1. Pentose phosphate pathway (PPP) and glutathione coupling: Glucose-6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGD), glutathione reductase (GR), glutathione (GSH), oxidized glutathione (GSSG), glutathione peroxidase (GPx).

Figure 2. Activity% versus [MIBI] regression analysis graphs for hG6PD in the presence of seven different MIBI concentrations.

Figure 3. Activity% versus [DTPA] regression analysis graphs for hG6PD in the presence of seven different DTPA concentrations.

Figure 4. Activity% versus [DMSA] regression analysis graphs for hG6PD in the presence of six different DMSA concentrations.

Figure 5. Activity% versus [MDP] regression analysis graphs for hG6PD in the presence of six different MDP concentrations.

Table 1. Purification scheme of hG6PD by 2′,5′-ADP sepharose 4B affinity gel chromatography.

Purification step	Activity (EU/ml)	Total volume (ml)	Protein (mg/ml)	Total Protein (mg)	Total Activity (EU)	Specific Activity (EU/mg)	Yield (%)	Purification factor
Hemolysate	0.42	30	41.2	1236	12.6	0.0102	100	1
Ammonium sulfate precipitation (35–65)%	1.12	8	1.38	11.04	8.96	0.811	71.11	79.5
2′,5′-ADP Sepharose 4B affinity chromatography	2.16	3	0.38	1.14	6.48	5.68	51.43	557

Table 2. IC₅₀ and predicated binding energy values of hG6PD inhibitors.

Cmp	Structure	IC50 (mM)	IFD scores (kcal/mol)
MIBI		0.056	–
DTPA		0.172	−8.821
DMSA		0.274	−9.061
MDP		0.175	−8.214

Figure 6. RMSD evolution of Cα of hG6PD in complexes with MDP, DTPA and DMSA compounds, and control system (upper panel) and also heavy atoms of three ligands into the active site (lower panel) during 10 ns MD simulation.

Figure 7. Protein–ligand interaction analysis of MDP, DTPA and DMSA into the ligand-binding pocket of hG6PD throughout the MD simulations.

Figure 8. 3D ligand interaction diagrams of studied compounds.