Format

Send to

Choose Destination
See comment in PubMed Commons below
Bioorg Med Chem Lett. 2014 Jul 1;24(13):2797-801. doi: 10.1016/j.bmcl.2014.04.117. Epub 2014 May 9.

Sulfonamide inhibition studies of the β carbonic anhydrase from Drosophila melanogaster.

Author information

1
School of Medicine, University of Tampere, Tampere, Finland; BioMediTech, University of Tampere, Tampere, Finland.
2
School of Medicine, University of Tampere, Tampere, Finland; BioMediTech, University of Tampere, Tampere, Finland; Fimlab Laboratories Ltd and Tampere University Hospital, Tampere, Finland.
3
Università degli Studi di Firenze, Dipartimento di Chimica, Laboratorio di Chimica Bioinorganica, Via della Lastruccia 3, 50019 Sesto Fiorentino (Firenze), Italy.
4
Università degli Studi di Firenze, Dipartimento di Chimica, Laboratorio di Chimica Bioinorganica, Via della Lastruccia 3, 50019 Sesto Fiorentino (Firenze), Italy; Università degli Studi di Firenze, Neurofarba Dipartment, Sezione di Scienza Farmaceutiche e Nutraceutiche, Via Ugo Sciff 6, 50019 Sesto Fiorentino (Firenze), Italy. Electronic address: claudiu.supuran@unifi.it.

Abstract

An inibition study of the β-carbonic anhydrase (CA, EC 4.2.1.1) DmBCA from the insect Drosophila melanogaster with sulfonamides and sulfamates is reported. Among the panel of 40 investigated compounds, the best DmBCA inhibitors were the sulfonylated benzenesulfonamides and ethoxzolamide, which showed inhibition constants in the range of 65.3-138 nM. Methazolamide and sulthiame were also effective inhibitors with KIs ranging between 237 and 249 nM, whereas most of the simple aromatic/heterocyclic sulfonamides showed inhibition constants in the range of 0.47-6.40 μM. Topiramate, zonisamide and saccharine did not inhibit DmBCA. As orthologs of this mitochondrial CA are found in many insect species involved in the spread of various diseases, inhibitors interfering with their activity may be of interest for developing insecticides with an alternative mechanism of action to the presently used agents, for which many insects developed extensive resistance.

KEYWORDS:

Carbonic anhydrase; Drosophila melanogaster; Enzyme inhibitor; Sulfonamide; β-Class enzyme

PMID:
24852120
DOI:
10.1016/j.bmcl.2014.04.117
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center