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o-Benzenedisulfonimido-sulfonamides are potent inhibitors of the tumor-associated carbonic anhydrase isoforms CA IX and CA XII.
Bioorg Med Chem. 2013 Mar 15; 21(6):1386-91.BM

Abstract

By using phthalimido-substituted aromatic sufonamides as lead molecules, a series of new sulfonamides incorporating ortho-benzenedisulfonimide moieties have been synthesized and tested against the human (h) cytosolic carbonic anhydrase (CA, EC 4.2.1.1) isozymes hCA I and hCA II and the transmembrane, tumor-associated isozymes hCA IX and hCA XII. All these compounds showed Ki values lower than 100nM and many of them showed better Kis than the reference compound acetazolamide, a clinically used sulfonamide. The tumor-associated isozymes were better inhibited than the cytosolic ones. A molecular docking within the active site of some CA isoforms, such as hCA I, explained these findings, as the benzenedisulfonimide moiety makes favorable interactions (hydrogen bonds) with amino acid residues involved in binding of inhibitors, such as Gln92, His67, and His64.

Authors+Show Affiliations

Istanbul University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, 34116 Beyazıt, Istanbul, Turkey.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

23352754

Citation

Güzel-Akdemir, Özlen, et al. "O-Benzenedisulfonimido-sulfonamides Are Potent Inhibitors of the Tumor-associated Carbonic Anhydrase Isoforms CA IX and CA XII." Bioorganic & Medicinal Chemistry, vol. 21, no. 6, 2013, pp. 1386-91.
Güzel-Akdemir Ö, Akdemir A, Isik S, et al. O-Benzenedisulfonimido-sulfonamides are potent inhibitors of the tumor-associated carbonic anhydrase isoforms CA IX and CA XII. Bioorg Med Chem. 2013;21(6):1386-91.
Güzel-Akdemir, Ö., Akdemir, A., Isik, S., Vullo, D., & Supuran, C. T. (2013). O-Benzenedisulfonimido-sulfonamides are potent inhibitors of the tumor-associated carbonic anhydrase isoforms CA IX and CA XII. Bioorganic & Medicinal Chemistry, 21(6), 1386-91. https://doi.org/10.1016/j.bmc.2012.12.037
Güzel-Akdemir Ö, et al. O-Benzenedisulfonimido-sulfonamides Are Potent Inhibitors of the Tumor-associated Carbonic Anhydrase Isoforms CA IX and CA XII. Bioorg Med Chem. 2013 Mar 15;21(6):1386-91. PubMed PMID: 23352754.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - o-Benzenedisulfonimido-sulfonamides are potent inhibitors of the tumor-associated carbonic anhydrase isoforms CA IX and CA XII. AU - Güzel-Akdemir,Özlen, AU - Akdemir,Atilla, AU - Isik,Semra, AU - Vullo,Daniela, AU - Supuran,Claudiu T, Y1 - 2013/01/04/ PY - 2012/11/26/received PY - 2012/12/24/revised PY - 2012/12/26/accepted PY - 2013/1/29/entrez PY - 2013/1/29/pubmed PY - 2013/9/5/medline SP - 1386 EP - 91 JF - Bioorganic & medicinal chemistry JO - Bioorg Med Chem VL - 21 IS - 6 N2 - By using phthalimido-substituted aromatic sufonamides as lead molecules, a series of new sulfonamides incorporating ortho-benzenedisulfonimide moieties have been synthesized and tested against the human (h) cytosolic carbonic anhydrase (CA, EC 4.2.1.1) isozymes hCA I and hCA II and the transmembrane, tumor-associated isozymes hCA IX and hCA XII. All these compounds showed Ki values lower than 100nM and many of them showed better Kis than the reference compound acetazolamide, a clinically used sulfonamide. The tumor-associated isozymes were better inhibited than the cytosolic ones. A molecular docking within the active site of some CA isoforms, such as hCA I, explained these findings, as the benzenedisulfonimide moiety makes favorable interactions (hydrogen bonds) with amino acid residues involved in binding of inhibitors, such as Gln92, His67, and His64. SN - 1464-3391 UR - https://www.unboundmedicine.com/medline/citation/23352754/o_Benzenedisulfonimido_sulfonamides_are_potent_inhibitors_of_the_tumor_associated_carbonic_anhydrase_isoforms_CA_IX_and_CA_XII_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0968-0896(12)01010-3 DB - PRIME DP - Unbound Medicine ER -