Some sulfonamide drugs inhibit ATPase activity of heat shock protein 90: investigation by docking simulation and experimental validation

Figures & data

Figure 1.  Chemical structures of tested sulfonamides.

Table 1.  Results of evaluated sulfonamides.

Drug	IC50 (µM) or % inhibition	pKa^b	Values of docking scoring functions^a
			Ligscore1^c	Ligscore2^c	−PLP1	−PLP2	Jain	−PMF	Consensus score
Torsemide	1.0 (0.94)^d	6.4	4.67	4.58	59.97	55.24	0.11	64.17	6^e
Sulfadiazine	1.5 (0.96)^d	6.5	4.17	3.89	55.53	49.24	2.62	52.8	6^e
Sulfathiazole	2.6 (0.99)^d	7.1	4.44	4.53	32.2	29.5	0.8	25.3	5^f
Sulfamethizole	50.1 (0.88)^g	5.5	4.21	4.9	36.1	31.31	1.13	31.0	6^f
Sulfisoxazole	60.7 (0.90)^g	5.0	3.67	4.62	46.5	40.13	−0.54	45.7	6^f
Sulfadoxine	25% at 100 µM	5.8	5.48	5.29	62.37	65.86	0.97	70.9	6^e
Sulfaguanide	11% at 100 µM	9.7	4.67	4.58	59.97	55.24	0.11	64.17	6^e
Sulfacetamide	9% at 100 µM	5.4	3.77	4.33	26	24.48	−0.38	32.9	4^f
Geldanamycin reference standard	272 nM (0.98)	—	—	—	—	—	—	—	—

^aSee references [45–51].

^bSee references [59,60].

^cCalculated using CFF force field.

^eFlexible docking.

^d,gValues in brackets represent the correlation coefficients of the corresponding dose–response lines determined over 3 or 4 concentration logarithmic cycles, respectively (i.e. 0.1, 1, 10, and 100 µM).

^fRigid docking.

Figure 2.  Docked poses of tested sulfonamides in Hsp90 (PDB code: 1YET, resolution 1.9 Å). (A) and (B) showing the binding pocket with and without solvent accessible surface, respectively.

Figure 3.  Docked poses of (A) torsemide and (B) sulfadiazine in Hsp90.

Figure 4.  Docked poses of (A) sulfacetamide and (B) sulfaguanide in Hsp90.

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