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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.
Bioorg Med Chem Lett. 2005 Jun 15; 15(12):3096-101.BM

Abstract

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.

Authors+Show Affiliations

Ospedale San Lazzaro, Divisione di Urologia, Via Pierino Belli 26, 12051 Alba, Cuneo, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15908204

Citation

Puccetti, Luca, et al. "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, vol. 15, no. 12, 2005, pp. 3096-101.
Puccetti L, Fasolis G, Vullo D, et al. 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. Bioorg Med Chem Lett. 2005;15(12):3096-101.
Puccetti, L., Fasolis, G., Vullo, D., Chohan, Z. H., Scozzafava, A., & Supuran, C. T. (2005). 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, 15(12), 3096-101.
Puccetti L, et al. 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. Bioorg Med Chem Lett. 2005 Jun 15;15(12):3096-101. PubMed PMID: 15908204.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Puccetti,Luca, AU - Fasolis,Giuseppe, AU - Vullo,Daniela, AU - Chohan,Zahid H, AU - Scozzafava,Andrea, AU - Supuran,Claudiu T, PY - 2005/02/01/received PY - 2005/03/31/revised PY - 2005/04/12/accepted PY - 2005/5/24/pubmed PY - 2005/9/20/medline PY - 2005/5/24/entrez SP - 3096 EP - 101 JF - Bioorganic & medicinal chemistry letters JO - Bioorg Med Chem Lett VL - 15 IS - 12 N2 - 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. SN - 0960-894X UR - https://www.unboundmedicine.com/medline/citation/15908204/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_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0960-894X(05)00540-8 DB - PRIME DP - Unbound Medicine ER -