Benzenesulfonamide bearing 1,2,4-triazole scaffolds as potent inhibitors of tumor associated carbonic anhydrase isoforms hCA IX and hCA XII.
Bioorg Med Chem. 2014 Mar 15; 22(6):1873-82.BM

Abstract

Three series of novel heterocyclic compounds (3a-3g, 4a-4g and 5a-5g) containing benzenesulfonamide moiety and incorporating a 1,2,4-triazole ring, have been synthesized and investigated as inhibitors against four isomers of the α-class carbonic anhydrases (CAs, EC 4.2.1.1), comprising hCAs I and II (cytosolic, ubiquitous isozymes) and hCAs IX and XII (transmembrane, tumor associated isozymes). Against the human isozymes hCA I and II, compounds of two series (3a-3g and 4a-4g) showed Ki values in the range of 84-868 nM and 5.6-390 nM, respectively whereas compounds of series 5a-5g were found to be poor inhibitors (Ki values exceeding 10,000 nM in some cases). Against hCA IX and XII, all the tested compounds exhibited excellent to moderate inhibitory potential with Ki values in the range of 2.8-431 nM and 1.3-63 nM, respectively. Compounds 3d, 3f and 4f exhibited excellent inhibitory potential against all of the four isozymes hCA I, II, IX and XII, even better than the standard drug acetazolamide (AZA) whereas compound of the series 5a-5g were comparatively less potent but more selective towards hCA IX and XII.

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Authors+Show Affiliations

SitaRam

Department of Chemistry, Kurukshetra University, Kurukshetra 136119, India.

Celik G

Chemistry Department, Balıkesir University, 10145 Balıkesir, Turkey.

Khloya P

Department of Chemistry, Kurukshetra University, Kurukshetra 136119, India.

Vullo D

Università degli Studi di Firenze, Polo Scientifico, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, 50019 Sesto Fiorentino, Florence, Italy.

Supuran CT

Università degli Studi di Firenze, Polo Scientifico, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, 50019 Sesto Fiorentino, Florence, Italy; Università degli Studi di Firenze, Neurofarba Dept., Section of Pharmaceutical and Nutraceutical Sciences, Via U. Schiff 6, 50019 Sesto Fiorentino, Florence, Italy. Electronic address: claudiu.supuran@unifi.it.

Sharma PK

Department of Chemistry, Kurukshetra University, Kurukshetra 136119, India. Electronic address: pksharma@kuk.ac.in.

MeSH

Carbonic Anhydrase InhibitorsCarbonic AnhydrasesDose-Response Relationship, DrugHumansIsoenzymesMolecular StructureStructure-Activity RelationshipSulfonamidesTriazoles

Pub Type(s)

Journal Article

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

Language

eng

PubMed ID

24560737

Citation

SitaRam, , et al. "Benzenesulfonamide Bearing 1,2,4-triazole Scaffolds as Potent Inhibitors of Tumor Associated Carbonic Anhydrase Isoforms hCA IX and hCA XII." Bioorganic & Medicinal Chemistry, vol. 22, no. 6, 2014, pp. 1873-82.

SitaRam , Celik G, Khloya P, et al. Benzenesulfonamide bearing 1,2,4-triazole scaffolds as potent inhibitors of tumor associated carbonic anhydrase isoforms hCA IX and hCA XII. Bioorg Med Chem. 2014;22(6):1873-82.

SitaRam, ., Celik, G., Khloya, P., Vullo, D., Supuran, C. T., & Sharma, P. K. (2014). Benzenesulfonamide bearing 1,2,4-triazole scaffolds as potent inhibitors of tumor associated carbonic anhydrase isoforms hCA IX and hCA XII. Bioorganic & Medicinal Chemistry, 22(6), 1873-82. https://doi.org/10.1016/j.bmc.2014.01.055

SitaRam , et al. Benzenesulfonamide Bearing 1,2,4-triazole Scaffolds as Potent Inhibitors of Tumor Associated Carbonic Anhydrase Isoforms hCA IX and hCA XII. Bioorg Med Chem. 2014 Mar 15;22(6):1873-82. PubMed PMID: 24560737.

* Article titles in AMA citation format should be in sentence-case

TY - JOUR T1 - Benzenesulfonamide bearing 1,2,4-triazole scaffolds as potent inhibitors of tumor associated carbonic anhydrase isoforms hCA IX and hCA XII. AU - SitaRam,, AU - Celik,Gulsah, AU - Khloya,Poonam, AU - Vullo,Daniela, AU - Supuran,Claudiu T, AU - Sharma,Pawan K, Y1 - 2014/02/07/ PY - 2013/12/05/received PY - 2014/01/27/revised PY - 2014/01/27/accepted PY - 2014/2/25/entrez PY - 2014/2/25/pubmed PY - 2014/12/15/medline KW - Acetazolamide KW - Benzenesulfonamide KW - Carbonic anhydrase isoforms I, II, IX, XII KW - Triazoles SP - 1873 EP - 82 JF - Bioorganic & medicinal chemistry JO - Bioorg Med Chem VL - 22 IS - 6 N2 - Three series of novel heterocyclic compounds (3a-3g, 4a-4g and 5a-5g) containing benzenesulfonamide moiety and incorporating a 1,2,4-triazole ring, have been synthesized and investigated as inhibitors against four isomers of the α-class carbonic anhydrases (CAs, EC 4.2.1.1), comprising hCAs I and II (cytosolic, ubiquitous isozymes) and hCAs IX and XII (transmembrane, tumor associated isozymes). Against the human isozymes hCA I and II, compounds of two series (3a-3g and 4a-4g) showed Ki values in the range of 84-868 nM and 5.6-390 nM, respectively whereas compounds of series 5a-5g were found to be poor inhibitors (Ki values exceeding 10,000 nM in some cases). Against hCA IX and XII, all the tested compounds exhibited excellent to moderate inhibitory potential with Ki values in the range of 2.8-431 nM and 1.3-63 nM, respectively. Compounds 3d, 3f and 4f exhibited excellent inhibitory potential against all of the four isozymes hCA I, II, IX and XII, even better than the standard drug acetazolamide (AZA) whereas compound of the series 5a-5g were comparatively less potent but more selective towards hCA IX and XII. SN - 1464-3391 UR - https://www.unboundmedicine.com/medline/citation/24560737/Benzenesulfonamide_bearing_124_triazole_scaffolds_as_potent_inhibitors_of_tumor_associated_carbonic_anhydrase_isoforms_hCA_IX_and_hCA_XII_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0968-0896(14)00092-3 DB - PRIME DP - Unbound Medicine ER -

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Benzenesulfonamide bearing 1,2,4-triazole scaffolds as potent inhibitors of tumor associated carbonic anhydrase isoforms hCA IX and hCA XII.Bioorg Med Chem. 2014 Mar 15; 22(6):1873-82.BM