title: Some sulfonamide drugs inhibit ATPase activity of heat shock protein 90: investigation by docking simulation and experimental validation.
abstract: Eight selected sulfonamide drugs were investigated as inhibitors of heat shock protein 90 (Hsp90). The investigation included simulated docking experiments to fit the selected compounds within the binding pocket of Hsp90. The selected molecules were found to readily fit within the ATP-binding pocket of Hsp90 in low-energy poses. The sulfonamides torsemide, sulfathiazole, and sulfadiazine were found to inhibit the ATPase activity of Hsp90 with IC(50) values of 1.0, 2.6, and 1.5 μM, respectively. Our results suggest that these well-established sulfonamides can be good leads for subsequent optimization into potent Hsp90 inhibitors.
authors.affiliation: Department of Pharmaceutical Sciences, Faculty of Pharmacy, Al-Zaytoonah Private University of Jordan, Amman, Jordan.
authors.forename: Ghassan Abu
authors.initials: GA
authors.lastname: Sheikha
authors.forename: Mahmoud A
authors.initials: MA
authors.lastname: Al-Sha'er
authors.forename: Mutasem O
authors.initials: MO
authors.lastname: Taha
mesh_terms: D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors*; D001681:Biological Assay; D004396:Coloring Agents / Q000737:chemistry; D003198:Computer Simulation; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D015394:Molecular Structure; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics; D015203:Reproducibility of Results; D012394:Rosaniline Dyes / Q000737:chemistry; D013414:Sulfaguanidine / Q000737:chemistry / Q000494:pharmacology; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D004396:Coloring Agents; D004791:Enzyme Inhibitors; D018841:HSP90 Heat-Shock Proteins; D011994:Recombinant Proteins; D012394:Rosaniline Dyes; D013449:Sulfonamides; C005095:malachite green; D013414:Sulfaguanidine; D000251:Adenosine Triphosphatases