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4-Functionalized 1,3-diarylpyrazoles bearing benzenesulfonamide moiety as selective potent inhibitors of the tumor associated carbonic anhydrase isoforms IX and XII.
Eur J Med Chem. 2014 Apr 09; 76:284-90.EJ

Abstract

A library of 4-functionalized 1,3-diarylpyrazoles (3a-3h, 5a-5g and 6a-6g) was designed, synthesized and evaluated against four human carbonic anhydrase (CA, EC 4.2.1.1) isozymes representing two cytosolic isozymes hCA I and hCA II, and two transmembrane tumor associated ones, hCA IX and hCA XII. All the twenty two tested compounds exhibited excellent CA activity profile against the four CA isozymes when compared to the reference drug acetazolamide. Six of the tested compounds (3a-3b, 3f, 3h, 6a and 6b) displayed low nanomolar affinity (Ki < 5 nM) for hCA IX whereas seven compounds (3a-3b, 3d-3f, 3h and 6f) displayed Ki < 10 nM against hCA XII. In addition, they acted as selective CA inhibitors of isoforms IX and XII over the physiological isoforms I and II.

Authors+Show Affiliations

Department of Chemistry, Kurukshetra University, Kurukshetra 136119, India.Chemistry Department, Balikesir University, 10145 Balikesir, Turkey.Department of Chemistry, Kurukshetra University, Kurukshetra 136119, India.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, 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.Department of Chemistry, Kurukshetra University, Kurukshetra 136119, India. Electronic address: pksharma@kuk.ac.in.

Pub Type(s)

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

Language

eng

PubMed ID

24589484

Citation

Khloya, Poonam, et al. "4-Functionalized 1,3-diarylpyrazoles Bearing Benzenesulfonamide Moiety as Selective Potent Inhibitors of the Tumor Associated Carbonic Anhydrase Isoforms IX and XII." European Journal of Medicinal Chemistry, vol. 76, 2014, pp. 284-90.
Khloya P, Celik G, SitaRam , et al. 4-Functionalized 1,3-diarylpyrazoles bearing benzenesulfonamide moiety as selective potent inhibitors of the tumor associated carbonic anhydrase isoforms IX and XII. Eur J Med Chem. 2014;76:284-90.
Khloya, P., Celik, G., SitaRam, ., Vullo, D., Supuran, C. T., & Sharma, P. K. (2014). 4-Functionalized 1,3-diarylpyrazoles bearing benzenesulfonamide moiety as selective potent inhibitors of the tumor associated carbonic anhydrase isoforms IX and XII. European Journal of Medicinal Chemistry, 76, 284-90. https://doi.org/10.1016/j.ejmech.2014.02.023
Khloya P, et al. 4-Functionalized 1,3-diarylpyrazoles Bearing Benzenesulfonamide Moiety as Selective Potent Inhibitors of the Tumor Associated Carbonic Anhydrase Isoforms IX and XII. Eur J Med Chem. 2014 Apr 9;76:284-90. PubMed PMID: 24589484.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 4-Functionalized 1,3-diarylpyrazoles bearing benzenesulfonamide moiety as selective potent inhibitors of the tumor associated carbonic anhydrase isoforms IX and XII. AU - Khloya,Poonam, AU - Celik,Gulsah, AU - SitaRam,, AU - Vullo,Daniela, AU - Supuran,Claudiu T, AU - Sharma,Pawan K, Y1 - 2014/02/11/ PY - 2013/12/03/received PY - 2014/02/05/revised PY - 2014/02/08/accepted PY - 2014/3/5/entrez PY - 2014/3/5/pubmed PY - 2014/12/15/medline KW - Acetazolamide KW - Benzenesulfonamide KW - Carbonic anhydrase isoforms I, II, IX, XII KW - Pyrazole SP - 284 EP - 90 JF - European journal of medicinal chemistry JO - Eur J Med Chem VL - 76 N2 - A library of 4-functionalized 1,3-diarylpyrazoles (3a-3h, 5a-5g and 6a-6g) was designed, synthesized and evaluated against four human carbonic anhydrase (CA, EC 4.2.1.1) isozymes representing two cytosolic isozymes hCA I and hCA II, and two transmembrane tumor associated ones, hCA IX and hCA XII. All the twenty two tested compounds exhibited excellent CA activity profile against the four CA isozymes when compared to the reference drug acetazolamide. Six of the tested compounds (3a-3b, 3f, 3h, 6a and 6b) displayed low nanomolar affinity (Ki < 5 nM) for hCA IX whereas seven compounds (3a-3b, 3d-3f, 3h and 6f) displayed Ki < 10 nM against hCA XII. In addition, they acted as selective CA inhibitors of isoforms IX and XII over the physiological isoforms I and II. SN - 1768-3254 UR - https://www.unboundmedicine.com/medline/citation/24589484/4_Functionalized_13_diarylpyrazoles_bearing_benzenesulfonamide_moiety_as_selective_potent_inhibitors_of_the_tumor_associated_carbonic_anhydrase_isoforms_IX_and_XII_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0223-5234(14)00143-3 DB - PRIME DP - Unbound Medicine ER -