Amido/ureidosubstituted benzenesulfonamides-isatin conjugates as low nanomolar/subnanomolar inhibitors of the tumor-associated carbonic anhydrase isoform XII

Wagdy M Eldehna; Mohamed Fares; Mariangela Ceruso; Hazem A Ghabbour; Sahar M Abou-Seri; Hatem A Abdel-Aziz; Dalal A Abou El Ella; Claudiu T Supuran

doi:10.1016/j.ejmech.2016.01.030

Amido/ureidosubstituted benzenesulfonamides-isatin conjugates as low nanomolar/subnanomolar inhibitors of the tumor-associated carbonic anhydrase isoform XII

Eur J Med Chem. 2016 Mar 3:110:259-66. doi: 10.1016/j.ejmech.2016.01.030. Epub 2016 Jan 20.

Authors

Wagdy M Eldehna¹, Mohamed Fares², Mariangela Ceruso³, Hazem A Ghabbour⁴, Sahar M Abou-Seri⁵, Hatem A Abdel-Aziz⁶, Dalal A Abou El Ella⁷, Claudiu T Supuran⁸

Affiliations

¹ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo, P.O. Box 11829, Egypt. Electronic address: wagdy2000@gmail.com.
² Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo, P.O. Box 11829, Egypt.
³ Department of Chemistry, Laboratory of Bioinorganic Chemistry, University of Florence, Polo Scientifico, Via della Lastruccia 3, 50019 Sesto Fiorentino Firenze, Italy.
⁴ Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
⁵ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo, P.O. Box 11562, Egypt.
⁶ Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia; Department of Applied Organic Chemistry, National Research Center, Dokki, Giza, P.O. Box 12622, Egypt.
⁷ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ain Shams University, Cairo, Abbassia, P.O. Box 11566, Egypt.
⁸ Department of Chemistry, Laboratory of Bioinorganic Chemistry, University of Florence, Polo Scientifico, Via della Lastruccia 3, 50019 Sesto Fiorentino Firenze, Italy; Department of NEUROFARBA, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Polo Scientifico, Via U. Schiff 6, 50019 Sesto Fiorentino, Firenze, Italy. Electronic address: claudiu.supuran@unifi.it.

PMID: 26840366
DOI: 10.1016/j.ejmech.2016.01.030

Abstract

By using a molecular hybridization approach, two series of amido/ureidosubstituted benzenesulfonamides incorporating substituted-isatin moieties were synthesized. The prepared derivatives were in vitro evaluated for their inhibitory activity against human carbonic anhydrase (hCA, EC 4.2.1.1) I, II (cytosolic) and IX, XII (transmembrane, tumor-associated) isoforms. All these isoforms were inhibited in variable degrees by the sulfonamides reported here. hCA I was inhibited with KIs in the range of 7.9-894 nM, hCA II in the range of 7.5-1645 nM (with one compound having a KI > 10 μM); hCA IX in the range of 5.0-240 nM, whereas hCA XII in the range of 0.47-2.83 nM. As all these isoforms are involved in various pathologies, in which their inhibition can be exploited therapeutically, the derivatives reported here may represent interesting extensions to the field of CA inhibitors of the sulfonamide type.

Keywords: Amido/ureido sulfonamides; Carbonic anhydrase; Isatin; Tumor-associated isoforms.

Publication types

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

MeSH terms

Benzenesulfonamides
Carbonic Anhydrase Inhibitors / chemical synthesis
Carbonic Anhydrase Inhibitors / chemistry*
Carbonic Anhydrase Inhibitors / pharmacology*
Carbonic Anhydrases / metabolism*
Humans
Isatin / chemical synthesis
Isatin / chemistry*
Isatin / pharmacology*
Protein Isoforms / antagonists & inhibitors
Protein Isoforms / metabolism
Structure-Activity Relationship
Sulfonamides / chemical synthesis
Sulfonamides / chemistry*
Sulfonamides / pharmacology*
Urea / analogs & derivatives
Urea / chemical synthesis
Urea / pharmacology

Substances

Carbonic Anhydrase Inhibitors
Protein Isoforms
Sulfonamides
Isatin
Urea
Carbonic Anhydrases
carbonic anhydrase XII