Ureidobenzenesulfonamides as efficient inhibitors of carbonic anhydrase II

Immo Serbian; Philipp Schwarzenberger; Anne Loesche; Sophie Hoenke; Ahmed Al-Harrasi; René Csuk

doi:10.1016/j.bioorg.2019.103123

Ureidobenzenesulfonamides as efficient inhibitors of carbonic anhydrase II

Bioorg Chem. 2019 Oct:91:103123. doi: 10.1016/j.bioorg.2019.103123. Epub 2019 Jul 17.

Authors

Immo Serbian¹, Philipp Schwarzenberger¹, Anne Loesche¹, Sophie Hoenke¹, Ahmed Al-Harrasi², René Csuk³

Affiliations

¹ Martin-Luther-University Halle-Wittenberg, Organic Chemistry, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), Germany.
² University of Nizwa, Chair of Oman's Medicinal Plants and Marine Natural Products, PO Box 33, Birkat Al-Mauz, Nizwa, Oman.
³ Martin-Luther-University Halle-Wittenberg, Organic Chemistry, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), Germany. Electronic address: rene.csuk@chemie.uni-halle.de.

PMID: 31336306
DOI: 10.1016/j.bioorg.2019.103123

Abstract

Sulfonamides represent an important class of drugs because of their inhibitory effect on carbonic anhydrases (CAs). We therefore synthesized several ureidobenzenesulfonamides and evaluated their bCA II inhibition for their potential use as anti-glaucoma gents. Since these compounds must not show cytotoxic effects, their cytotoxic potential against several human tumor cell lines and non-malignant fibroblasts was investigated. Several fluorophenyl substituted sulfonamides were efficient inhibitors of bCA II. Only one benzylphenyl substituted sulfonamide, however, showed a remarkable selectivity for HT29 colorectal carcinoma cells while being significantly less cytotoxic to non-malignant fibroblasts.

Keywords: Carbonic anhydrase; Glaucoma; Inhibitor; Urea; Ureidobenzenesulfonamide.

Publication types

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

MeSH terms

Animals
Carbonic Anhydrase II / antagonists & inhibitors*
Carbonic Anhydrase II / chemistry
Carbonic Anhydrase II / metabolism
Carbonic Anhydrase Inhibitors / chemical synthesis
Carbonic Anhydrase Inhibitors / metabolism
Carbonic Anhydrase Inhibitors / pharmacology*
Carbonic Anhydrase Inhibitors / toxicity
Catalytic Domain
Cattle
Glaucoma / drug therapy
HT29 Cells
Humans
Molecular Docking Simulation
Phenylurea Compounds / chemical synthesis
Phenylurea Compounds / metabolism
Phenylurea Compounds / pharmacology*
Phenylurea Compounds / toxicity
Protein Binding
Sulfonamides / chemical synthesis
Sulfonamides / metabolism
Sulfonamides / pharmacology*
Sulfonamides / toxicity

Substances

Carbonic Anhydrase Inhibitors
Phenylurea Compounds
Sulfonamides
Carbonic Anhydrase II