Flow synthesis and biological activity of aryl sulfonamides as selective carbonic anhydrase IX and XII inhibitors

Emiliano Rosatelli; Andrea Carotti; Mariangela Ceruso; Claudiu T Supuran; Antimo Gioiello

doi:10.1016/j.bmcl.2014.05.086

Flow synthesis and biological activity of aryl sulfonamides as selective carbonic anhydrase IX and XII inhibitors

Bioorg Med Chem Lett. 2014 Aug 1;24(15):3422-5. doi: 10.1016/j.bmcl.2014.05.086. Epub 2014 Jun 4.

Authors

Emiliano Rosatelli¹, Andrea Carotti¹, Mariangela Ceruso², Claudiu T Supuran³, Antimo Gioiello⁴

Affiliations

¹ Laboratory of Medicinal and Advanced Synthetic Chemistry (Lab MASC), Department of Pharmaceutical Sciences, University of Perugia, Via del Liceo 1, Perugia I-06123, Italy.
² Laboratory of Bioinorganic Chemistry, University of Florence, Via della Lastruccia 3, Sesto Fiorentino (Firenze) I-50019, Italy.
³ Neurofarba Dept., Section of Pharmaceutical and Nutriceutical Sciences, University of Florence, Via U. Schiff 6, Sesto Fiorentino (Firenze) I-50019, Italy.
⁴ Laboratory of Medicinal and Advanced Synthetic Chemistry (Lab MASC), Department of Pharmaceutical Sciences, University of Perugia, Via del Liceo 1, Perugia I-06123, Italy. Electronic address: antimo.gioiello@unipg.it.

PMID: 24948563
DOI: 10.1016/j.bmcl.2014.05.086

Abstract

A series of secondary and tertiary aryl sulfonamides were synthesized under flow conditions and evaluated for their ability to selectively inhibit tumor-associated carbonic anhydrase isoforms IX and XII. The tested compounds revealed to be highly potent CA IX inhibitors in nanomolar range, and to inhibit CA XII activity with different ranks of potencies. Remarkably, 4-methyl-N-phenyl-benzenesulfonamide was a selective nanomolar CA IX inhibitor with an IC50 of 90 nM.

Keywords: Carbonic anhydrases; Docking; Flow synthesis; Sulfonamides.

MeSH terms

Antigens, Neoplasm / metabolism*
Carbonic Anhydrase IX
Carbonic Anhydrase Inhibitors / chemical synthesis
Carbonic Anhydrase Inhibitors / chemistry
Carbonic Anhydrase Inhibitors / pharmacology*
Carbonic Anhydrases / metabolism*
Dose-Response Relationship, Drug
Humans
Models, Molecular
Molecular Structure
Structure-Activity Relationship
Sulfonamides / chemical synthesis
Sulfonamides / chemistry
Sulfonamides / pharmacology*

Substances

Antigens, Neoplasm
Carbonic Anhydrase Inhibitors
Sulfonamides
CA9 protein, human
Carbonic Anhydrase IX
Carbonic Anhydrases
carbonic anhydrase XII