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Carbonic anhydrase inhibitors. Synthesis, molecular structures, and inhibition of the human cytosolic isozymes I and II and transmembrane isozymes IX, XII (cancer-associated) and XIV with novel 3-pyridinesulfonamide derivatives.
Eur J Med Chem. 2011 Sep; 46(9):4403-10.EJ

Abstract

A series of novel 3-pyridinesulfonamide derivatives (2-5, 9-11 and 13-15) have been synthesized and investigated as inhibitors of five isoforms of zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1), that is, the cytosolic ubiquitous CA I and II, and isozymes CA IX and XII (cancer-associated), and XIV. Against the human isozyme hCA I the new compounds showed K(I)s in the range of 0.089-251 μM, whereas toward hCA II, K(I)s = 50.5-487 nM. Isozyme hCA IX was inhibited with K(I)s in the range of 5.2-18.3 nM, while hCA XII with K(I)s = 6.0-16.4 nM, and hCA XIV with K(I)s = 76.4-152.0 nM. All of the new compounds 2-5, 9-11 and 13-15 showed excellent hCA IX inhibitory efficacy, with K(I)s = 5.2-18.3 nM, being much more effective as compared to the clinically used AAZ, MZA, EZA, DCP and IND (K(I)s = 24-50 nM).

Authors+Show Affiliations

Department of Organic Chemistry, Medical University of Gdańsk, Al Gen J Hallera 107, 80-416 Gdańsk, Poland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

21820216

Citation

Brzozowski, Zdzisław, et al. "Carbonic Anhydrase Inhibitors. Synthesis, Molecular Structures, and Inhibition of the Human Cytosolic Isozymes I and II and Transmembrane Isozymes IX, XII (cancer-associated) and XIV With Novel 3-pyridinesulfonamide Derivatives." European Journal of Medicinal Chemistry, vol. 46, no. 9, 2011, pp. 4403-10.
Brzozowski Z, Sławiński J, Gdaniec M, et al. Carbonic anhydrase inhibitors. Synthesis, molecular structures, and inhibition of the human cytosolic isozymes I and II and transmembrane isozymes IX, XII (cancer-associated) and XIV with novel 3-pyridinesulfonamide derivatives. Eur J Med Chem. 2011;46(9):4403-10.
Brzozowski, Z., Sławiński, J., Gdaniec, M., Innocenti, A., & Supuran, C. T. (2011). Carbonic anhydrase inhibitors. Synthesis, molecular structures, and inhibition of the human cytosolic isozymes I and II and transmembrane isozymes IX, XII (cancer-associated) and XIV with novel 3-pyridinesulfonamide derivatives. European Journal of Medicinal Chemistry, 46(9), 4403-10. https://doi.org/10.1016/j.ejmech.2011.07.011
Brzozowski Z, et al. Carbonic Anhydrase Inhibitors. Synthesis, Molecular Structures, and Inhibition of the Human Cytosolic Isozymes I and II and Transmembrane Isozymes IX, XII (cancer-associated) and XIV With Novel 3-pyridinesulfonamide Derivatives. Eur J Med Chem. 2011;46(9):4403-10. PubMed PMID: 21820216.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Carbonic anhydrase inhibitors. Synthesis, molecular structures, and inhibition of the human cytosolic isozymes I and II and transmembrane isozymes IX, XII (cancer-associated) and XIV with novel 3-pyridinesulfonamide derivatives. AU - Brzozowski,Zdzisław, AU - Sławiński,Jarosław, AU - Gdaniec,Maria, AU - Innocenti,Alessio, AU - Supuran,Claudiu T, Y1 - 2011/07/08/ PY - 2011/04/27/received PY - 2011/06/29/revised PY - 2011/07/02/accepted PY - 2011/8/9/entrez PY - 2011/8/9/pubmed PY - 2012/1/4/medline SP - 4403 EP - 10 JF - European journal of medicinal chemistry JO - Eur J Med Chem VL - 46 IS - 9 N2 - A series of novel 3-pyridinesulfonamide derivatives (2-5, 9-11 and 13-15) have been synthesized and investigated as inhibitors of five isoforms of zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1), that is, the cytosolic ubiquitous CA I and II, and isozymes CA IX and XII (cancer-associated), and XIV. Against the human isozyme hCA I the new compounds showed K(I)s in the range of 0.089-251 μM, whereas toward hCA II, K(I)s = 50.5-487 nM. Isozyme hCA IX was inhibited with K(I)s in the range of 5.2-18.3 nM, while hCA XII with K(I)s = 6.0-16.4 nM, and hCA XIV with K(I)s = 76.4-152.0 nM. All of the new compounds 2-5, 9-11 and 13-15 showed excellent hCA IX inhibitory efficacy, with K(I)s = 5.2-18.3 nM, being much more effective as compared to the clinically used AAZ, MZA, EZA, DCP and IND (K(I)s = 24-50 nM). SN - 1768-3254 UR - https://www.unboundmedicine.com/medline/citation/21820216/Carbonic_anhydrase_inhibitors__Synthesis_molecular_structures_and_inhibition_of_the_human_cytosolic_isozymes_I_and_II_and_transmembrane_isozymes_IX_XII__cancer_associated__and_XIV_with_novel_3_pyridinesulfonamide_derivatives_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0223-5234(11)00524-1 DB - PRIME DP - Unbound Medicine ER -