The Experts below are selected from a list of 9 Experts worldwide ranked by ideXlab platform
Claudiu T Supuran - One of the best experts on this subject based on the ideXlab platform.
-
carbonic anhydrase inhibitors binding of an antiglaucoma glycosyl Sulfanilamide Derivative to human isoform ii and its consequences for the drug design of enzyme inhibitors incorporating sugar moieties
Bioorganic & Medicinal Chemistry Letters, 2007Co-Authors: Anna Di Fiore, Andrea Scozzafava, Jeanyves Winum, Jeanlouis Montero, Carlo Pedone, Claudiu T Supuran, Giuseppina De SimoneAbstract:Abstract N -(4-Sulfamoylphenyl)-α- d -glucopyranosylamine, a promising topical antiglaucoma agent, is a potent inhibitor of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1). The high resolution X-ray crystal structure of its adduct with the target isoform involved in glaucoma, CA II, is reported here. The sugar Sulfanilamide Derivative binds to the enzyme in a totally new manner as compared to other CA–inhibitor adducts investigated earlier. The sulfonamide anchor was coordinated to the active site metal ion, and the phenylene ring of the inhibitor filled the channel leading to the active site cavity. The glycosyl moiety responsible for the high water solubility of the compound was oriented towards a hydrophilic region of the active site, where no other inhibitors were observed to be bound up to now. A network of seven hydrogen bonds with four water molecules and the amino acid residues Pro201, Pro202 and Gln92 further stabilize the enzyme–inhibitor adduct. Topiramate, another sugar-based CA inhibitor, binds in a completely different manner to CA II as compared to the sulfonamide investigated here. These findings are useful for the design of potent, sugar-derived enzyme inhibitors.
-
carbonic anhydrase inhibitors inhibition of cytosolic tumor associated carbonic anhydrase isozymes i ii ix and xii with schiff s bases incorporating chromone and aromatic sulfonamide moieties and their zinc complexes
Bioorganic & Medicinal Chemistry Letters, 2005Co-Authors: Luca Puccetti, Andrea Scozzafava, G Fasolis, Daniela Vullo, Zahid H Chohan, Claudiu T SupuranAbstract:A series of Schiff's bases was prepared by reaction of 3-formyl-chromone or 6-methyl-3-formyl-chromone with aromatic sulfonamides, such as Sulfanilamide, homoSulfanilamide, 4-aminoethyl-benzenesulfonamide, a pyrimidinyl-substituted Sulfanilamide Derivative, sulfaguanidine and 4-amino-6-trifluoromethyl-benzene-1,3-disulfonamide. The zinc complexes of these sulfonamides have also been obtained. The new Derivatives and their Zn(II) complexes were investigated for the inhibition of four physiologically relevant isozymes of carbonic anhydrase (CA, EC 4.2.1.1): the cytosolic isoforms I and II, as well as the tumor-associated, transmembrane isozymes CA IX and XII. Except for the sulfaguanidine-derived compounds which were devoid of activity against all isozymes, the other sulfonamides and their metal complexes showed interesting inhibitory activity. Against isozyme CA I, the inhibition constants were in the range of 13-100 nM, against isozyme CA II in the range of 1.9-102 nM, against isozyme CA IX in the range of 6.3-48nM, and against CA XII in the range of 5.9-50nM. Generally, the formyl-chromone derived compounds were better CA inhibitors as compared to the corresponding 6-methyl-chromone Derivatives, and for the simple, benzenesulfonamide Derivatives activity increased with an increase of the spacer from Sulfanilamide to homoSulfanilamide and 4-aminoethylbenzenesulfonamide Derivatives, respectively. Some of these compounds may show applications for the development of therapies targeting hypoxic tumors in which CA IX and XII are often highly overexpressed.
Giuseppina De Simone - One of the best experts on this subject based on the ideXlab platform.
-
carbonic anhydrase inhibitors binding of an antiglaucoma glycosyl Sulfanilamide Derivative to human isoform ii and its consequences for the drug design of enzyme inhibitors incorporating sugar moieties
Bioorganic & Medicinal Chemistry Letters, 2007Co-Authors: Anna Di Fiore, Andrea Scozzafava, Jeanyves Winum, Jeanlouis Montero, Carlo Pedone, Claudiu T Supuran, Giuseppina De SimoneAbstract:Abstract N -(4-Sulfamoylphenyl)-α- d -glucopyranosylamine, a promising topical antiglaucoma agent, is a potent inhibitor of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1). The high resolution X-ray crystal structure of its adduct with the target isoform involved in glaucoma, CA II, is reported here. The sugar Sulfanilamide Derivative binds to the enzyme in a totally new manner as compared to other CA–inhibitor adducts investigated earlier. The sulfonamide anchor was coordinated to the active site metal ion, and the phenylene ring of the inhibitor filled the channel leading to the active site cavity. The glycosyl moiety responsible for the high water solubility of the compound was oriented towards a hydrophilic region of the active site, where no other inhibitors were observed to be bound up to now. A network of seven hydrogen bonds with four water molecules and the amino acid residues Pro201, Pro202 and Gln92 further stabilize the enzyme–inhibitor adduct. Topiramate, another sugar-based CA inhibitor, binds in a completely different manner to CA II as compared to the sulfonamide investigated here. These findings are useful for the design of potent, sugar-derived enzyme inhibitors.
Andrea Scozzafava - One of the best experts on this subject based on the ideXlab platform.
-
carbonic anhydrase inhibitors binding of an antiglaucoma glycosyl Sulfanilamide Derivative to human isoform ii and its consequences for the drug design of enzyme inhibitors incorporating sugar moieties
Bioorganic & Medicinal Chemistry Letters, 2007Co-Authors: Anna Di Fiore, Andrea Scozzafava, Jeanyves Winum, Jeanlouis Montero, Carlo Pedone, Claudiu T Supuran, Giuseppina De SimoneAbstract:Abstract N -(4-Sulfamoylphenyl)-α- d -glucopyranosylamine, a promising topical antiglaucoma agent, is a potent inhibitor of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1). The high resolution X-ray crystal structure of its adduct with the target isoform involved in glaucoma, CA II, is reported here. The sugar Sulfanilamide Derivative binds to the enzyme in a totally new manner as compared to other CA–inhibitor adducts investigated earlier. The sulfonamide anchor was coordinated to the active site metal ion, and the phenylene ring of the inhibitor filled the channel leading to the active site cavity. The glycosyl moiety responsible for the high water solubility of the compound was oriented towards a hydrophilic region of the active site, where no other inhibitors were observed to be bound up to now. A network of seven hydrogen bonds with four water molecules and the amino acid residues Pro201, Pro202 and Gln92 further stabilize the enzyme–inhibitor adduct. Topiramate, another sugar-based CA inhibitor, binds in a completely different manner to CA II as compared to the sulfonamide investigated here. These findings are useful for the design of potent, sugar-derived enzyme inhibitors.
-
carbonic anhydrase inhibitors inhibition of cytosolic tumor associated carbonic anhydrase isozymes i ii ix and xii with schiff s bases incorporating chromone and aromatic sulfonamide moieties and their zinc complexes
Bioorganic & Medicinal Chemistry Letters, 2005Co-Authors: Luca Puccetti, Andrea Scozzafava, G Fasolis, Daniela Vullo, Zahid H Chohan, Claudiu T SupuranAbstract:A series of Schiff's bases was prepared by reaction of 3-formyl-chromone or 6-methyl-3-formyl-chromone with aromatic sulfonamides, such as Sulfanilamide, homoSulfanilamide, 4-aminoethyl-benzenesulfonamide, a pyrimidinyl-substituted Sulfanilamide Derivative, sulfaguanidine and 4-amino-6-trifluoromethyl-benzene-1,3-disulfonamide. The zinc complexes of these sulfonamides have also been obtained. The new Derivatives and their Zn(II) complexes were investigated for the inhibition of four physiologically relevant isozymes of carbonic anhydrase (CA, EC 4.2.1.1): the cytosolic isoforms I and II, as well as the tumor-associated, transmembrane isozymes CA IX and XII. Except for the sulfaguanidine-derived compounds which were devoid of activity against all isozymes, the other sulfonamides and their metal complexes showed interesting inhibitory activity. Against isozyme CA I, the inhibition constants were in the range of 13-100 nM, against isozyme CA II in the range of 1.9-102 nM, against isozyme CA IX in the range of 6.3-48nM, and against CA XII in the range of 5.9-50nM. Generally, the formyl-chromone derived compounds were better CA inhibitors as compared to the corresponding 6-methyl-chromone Derivatives, and for the simple, benzenesulfonamide Derivatives activity increased with an increase of the spacer from Sulfanilamide to homoSulfanilamide and 4-aminoethylbenzenesulfonamide Derivatives, respectively. Some of these compounds may show applications for the development of therapies targeting hypoxic tumors in which CA IX and XII are often highly overexpressed.
Anna Di Fiore - One of the best experts on this subject based on the ideXlab platform.
-
carbonic anhydrase inhibitors binding of an antiglaucoma glycosyl Sulfanilamide Derivative to human isoform ii and its consequences for the drug design of enzyme inhibitors incorporating sugar moieties
Bioorganic & Medicinal Chemistry Letters, 2007Co-Authors: Anna Di Fiore, Andrea Scozzafava, Jeanyves Winum, Jeanlouis Montero, Carlo Pedone, Claudiu T Supuran, Giuseppina De SimoneAbstract:Abstract N -(4-Sulfamoylphenyl)-α- d -glucopyranosylamine, a promising topical antiglaucoma agent, is a potent inhibitor of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1). The high resolution X-ray crystal structure of its adduct with the target isoform involved in glaucoma, CA II, is reported here. The sugar Sulfanilamide Derivative binds to the enzyme in a totally new manner as compared to other CA–inhibitor adducts investigated earlier. The sulfonamide anchor was coordinated to the active site metal ion, and the phenylene ring of the inhibitor filled the channel leading to the active site cavity. The glycosyl moiety responsible for the high water solubility of the compound was oriented towards a hydrophilic region of the active site, where no other inhibitors were observed to be bound up to now. A network of seven hydrogen bonds with four water molecules and the amino acid residues Pro201, Pro202 and Gln92 further stabilize the enzyme–inhibitor adduct. Topiramate, another sugar-based CA inhibitor, binds in a completely different manner to CA II as compared to the sulfonamide investigated here. These findings are useful for the design of potent, sugar-derived enzyme inhibitors.
Jeanyves Winum - One of the best experts on this subject based on the ideXlab platform.
-
carbonic anhydrase inhibitors binding of an antiglaucoma glycosyl Sulfanilamide Derivative to human isoform ii and its consequences for the drug design of enzyme inhibitors incorporating sugar moieties
Bioorganic & Medicinal Chemistry Letters, 2007Co-Authors: Anna Di Fiore, Andrea Scozzafava, Jeanyves Winum, Jeanlouis Montero, Carlo Pedone, Claudiu T Supuran, Giuseppina De SimoneAbstract:Abstract N -(4-Sulfamoylphenyl)-α- d -glucopyranosylamine, a promising topical antiglaucoma agent, is a potent inhibitor of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1). The high resolution X-ray crystal structure of its adduct with the target isoform involved in glaucoma, CA II, is reported here. The sugar Sulfanilamide Derivative binds to the enzyme in a totally new manner as compared to other CA–inhibitor adducts investigated earlier. The sulfonamide anchor was coordinated to the active site metal ion, and the phenylene ring of the inhibitor filled the channel leading to the active site cavity. The glycosyl moiety responsible for the high water solubility of the compound was oriented towards a hydrophilic region of the active site, where no other inhibitors were observed to be bound up to now. A network of seven hydrogen bonds with four water molecules and the amino acid residues Pro201, Pro202 and Gln92 further stabilize the enzyme–inhibitor adduct. Topiramate, another sugar-based CA inhibitor, binds in a completely different manner to CA II as compared to the sulfonamide investigated here. These findings are useful for the design of potent, sugar-derived enzyme inhibitors.
