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Sulfonamide bearing pyrazolylpyrazolines as potent inhibitors of carbonic anhydrase isoforms I, II, IX and XII.
Bioorg Med Chem Lett. 2015 Aug 15; 25(16):3208-12.BM

Abstract

A series of pyrazolylpyrazolines was designed, synthesized and evaluated for carbonic anhydrase (CA, EC 4.2.1.1) inhibitory activity against cytosolic human (h) isozymes hCA I and hCA II as well as transmembrane tumor associated isozymes, hCA IX and hCA XII. All the tested compounds exhibited an excellent CA activity profile against hCA I, hCA II and hCA XII when compared to the reference drug acetazolamide (AZA). Compounds 6d, 6f and 7a-7f have exhibited better inhibition profile against hCA XII (Ki = 0.47-5.1 nM) as compared with AZA (Ki = 5.7 nM) especially, compounds 6a, 7a, 7c and 7d which were nearly 10-fold better than reference drug. Against hCA II, all of the tested compounds were better than the standard drug especially compounds 6c, 6d, 7c and 7d (Ki = 1.1-1.7 nM) were many fold better inhibitors than AZA (Ki = 12.1 nM). In addition, they acted as selective CA inhibitors of isoform hCA XII over the physiological isoform hCA I.

Authors+Show Affiliations

Department of Chemistry, Kurukshetra University, Kurukshetra 136119, India.Università degli Studi di Firenze, Laboratorio di Chimica Bioinorganica, Rm 188, and Neurofarba Department, Sezione di Scienze Farmaceutiche, Via U. Schiff 6, I-50019 Sesto Fiorentino (Firenze), Italy.Department of Chemistry, Kurukshetra University, Kurukshetra 136119, India.Università degli Studi di Firenze, Laboratorio di Chimica Bioinorganica, Rm 188, and Neurofarba Department, Sezione di Scienze Farmaceutiche, Via U. Schiff 6, I-50019 Sesto Fiorentino (Firenze), 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

26105196

Citation

Khloya, Poonam, et al. "Sulfonamide Bearing Pyrazolylpyrazolines as Potent Inhibitors of Carbonic Anhydrase Isoforms I, II, IX and XII." Bioorganic & Medicinal Chemistry Letters, vol. 25, no. 16, 2015, pp. 3208-12.
Khloya P, Ceruso M, Ram S, et al. Sulfonamide bearing pyrazolylpyrazolines as potent inhibitors of carbonic anhydrase isoforms I, II, IX and XII. Bioorg Med Chem Lett. 2015;25(16):3208-12.
Khloya, P., Ceruso, M., Ram, S., Supuran, C. T., & Sharma, P. K. (2015). Sulfonamide bearing pyrazolylpyrazolines as potent inhibitors of carbonic anhydrase isoforms I, II, IX and XII. Bioorganic & Medicinal Chemistry Letters, 25(16), 3208-12. https://doi.org/10.1016/j.bmcl.2015.05.096
Khloya P, et al. Sulfonamide Bearing Pyrazolylpyrazolines as Potent Inhibitors of Carbonic Anhydrase Isoforms I, II, IX and XII. Bioorg Med Chem Lett. 2015 Aug 15;25(16):3208-12. PubMed PMID: 26105196.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sulfonamide bearing pyrazolylpyrazolines as potent inhibitors of carbonic anhydrase isoforms I, II, IX and XII. AU - Khloya,Poonam, AU - Ceruso,Mariangela, AU - Ram,Sita, AU - Supuran,Claudiu T, AU - Sharma,Pawan K, Y1 - 2015/06/14/ PY - 2015/01/23/received PY - 2015/05/14/revised PY - 2015/05/28/accepted PY - 2015/6/25/entrez PY - 2015/6/25/pubmed PY - 2016/4/14/medline KW - Acetazolamide KW - Carbonic anhydrase isoforms I, II, IX, XII KW - Pyrazoles SP - 3208 EP - 12 JF - Bioorganic & medicinal chemistry letters JO - Bioorg Med Chem Lett VL - 25 IS - 16 N2 - A series of pyrazolylpyrazolines was designed, synthesized and evaluated for carbonic anhydrase (CA, EC 4.2.1.1) inhibitory activity against cytosolic human (h) isozymes hCA I and hCA II as well as transmembrane tumor associated isozymes, hCA IX and hCA XII. All the tested compounds exhibited an excellent CA activity profile against hCA I, hCA II and hCA XII when compared to the reference drug acetazolamide (AZA). Compounds 6d, 6f and 7a-7f have exhibited better inhibition profile against hCA XII (Ki = 0.47-5.1 nM) as compared with AZA (Ki = 5.7 nM) especially, compounds 6a, 7a, 7c and 7d which were nearly 10-fold better than reference drug. Against hCA II, all of the tested compounds were better than the standard drug especially compounds 6c, 6d, 7c and 7d (Ki = 1.1-1.7 nM) were many fold better inhibitors than AZA (Ki = 12.1 nM). In addition, they acted as selective CA inhibitors of isoform hCA XII over the physiological isoform hCA I. SN - 1464-3405 UR - https://www.unboundmedicine.com/medline/citation/26105196/Sulfonamide_bearing_pyrazolylpyrazolines_as_potent_inhibitors_of_carbonic_anhydrase_isoforms_I_II_IX_and_XII_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0960-894X(15)00579-X DB - PRIME DP - Unbound Medicine ER -