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).
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MeSH
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
L2 - https://linkinghub.elsevier.com/retrieve/pii/S0223-5234(11)00524-1
DB - PRIME
DP - Unbound Medicine
ER -
