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Bioorg Med Chem Lett. 2014 Nov 15;24(22):5185-9. doi: 10.1016/j.bmcl.2014.09.076. Epub 2014 Oct 2.

Carbonic anhydrase inhibitory activity of sulfonamides and carboxylic acids incorporating cyclic imide scaffolds.

Author information

1
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia; Department of Medicinal Chemistry, Faculty of Pharmacy, University of Mansoura, Mansoura 35516, Egypt. Electronic address: alaa_moenes@yahoo.com.
2
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia; Department of Organic Chemistry, Faculty of Pharmacy, Al-Azhar University, Cairo 11884, Egypt.
3
University of Florence, Neurofarba Department, Sezione di Scienze farmaceutiche, Via Ugo Schiff 6, 50019 Sesto Fiorentino (Florence), Italy.
4
University of Florence, Neurofarba Department, Sezione di Scienze farmaceutiche, Via Ugo Schiff 6, 50019 Sesto Fiorentino (Florence), Italy. Electronic address: claudiu.supuran@unifi.it.

Abstract

A series of sulfonamides incorporating cyclic imide moieties were investigated as inhibitors of several human α-carbonic anhydrase (hCA, EC 4.2.1.1) isoforms. Several carboxylic acids possessing the same scaffolds as the sulfonamides were also included in the study, since the sulfonamidate and the carboxylate are among the frequently used zinc-binding groups (ZBGs) for obtaining zinc enzymes inhibitors. The cytosolic isoform hCA I was moderately inhibited by most of the 30 investigated derivatives; many low nanomolar hCA II inhibitors were detected, whereas some of these compounds were low nanomolar/subnanomolar inhibitors of the transmembrane, tumor-associated isoforms hCA IX and XII. In this series of compounds the SO(2)NH(-) and the COO(-) ZBGs showed similar efficacy for obtaining potent inhibitors, although some carboxylates had isoform-selective inhibition profiles for the transmembrane CAs.

KEYWORDS:

Carbonic anhydrase; Carboxylic acid; Inhibitor; Isoform-selective inhibitor; Sulfonamide; Zinc-binding groups

PMID:
25442309
DOI:
10.1016/j.bmcl.2014.09.076
[Indexed for MEDLINE]

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