Benedetta Cornelio
4-Arylbenzenesulfonamides as Human Carbonic Anhydrase Inhibitors (hCAIs): Synthesis by Pd Nanocatalyst-Mediated Suzuki–Miyaura Reaction, Enzyme Inhibition, and X-ray Crystallographic Studies
Cornelio, Benedetta; Laronze-Cochard, Marie; Ceruso, Mariangela; Ferraroni, Marta; Rance, Graham A.; Carta, Fabrizio; Khlobystov, Andrei N.; Fontana, Antonella; Supuran, Claudiu T.; Sapi, Janos
Authors
Marie Laronze-Cochard
Mariangela Ceruso
Marta Ferraroni
GRAHAM RANCE Graham.Rance@nottingham.ac.uk
Senior Research Fellow
Fabrizio Carta
ANDREI KHLOBYSTOV ANDREI.KHLOBYSTOV@NOTTINGHAM.AC.UK
Professor of Chemical Nanoscience
Antonella Fontana
Claudiu T. Supuran
Janos Sapi
Abstract
Benzenesulfonamides bearing various substituted (hetero)aryl rings in the para-position were prepared by palladium nanoparticle-catalyzed Suzuki–Miyaura cross-coupling reactions and evaluated as human carbonic anhydrase (hCA, EC 4.2.1.1) inhibitors against isoforms hCA I, II, IX, and XII. Most of the prepared sulfonamides showed low inhibition against hCA I isoform, whereas the other cytosolic isoenzyme, hCA II, was strongly affected. The major part of these new derivatives acted as potent inhibitors of the tumor-associated isoform hCA XII. An opposite trend was observed for phenyl, naphthyl, and various heteroaryl substituted benzenesulfonamides which displayed subnanomolar hCA IX inhibition while poorly inhibiting the other tumor-associated isoform hCA XII. The inhibition potency and influence of the partially restricted aryl–aryl bond rotation on the activity/selectivity were rationalized by means of X-ray crystallography of the adducts of hCA II with several 4-arylbenzenesulfonamides.
Citation
Cornelio, B., Laronze-Cochard, M., Ceruso, M., Ferraroni, M., Rance, G. A., Carta, F., …Sapi, J. (2016). 4-Arylbenzenesulfonamides as Human Carbonic Anhydrase Inhibitors (hCAIs): Synthesis by Pd Nanocatalyst-Mediated Suzuki–Miyaura Reaction, Enzyme Inhibition, and X-ray Crystallographic Studies. Journal of Medicinal Chemistry, 59(2), 721-732. https://doi.org/10.1021/acs.jmedchem.5b01771
Journal Article Type | Article |
---|---|
Acceptance Date | Jan 7, 2016 |
Online Publication Date | Jan 15, 2016 |
Publication Date | Jan 28, 2016 |
Deposit Date | Aug 18, 2020 |
Publicly Available Date | Sep 14, 2020 |
Journal | Journal of Medicinal Chemistry |
Print ISSN | 0022-2623 |
Electronic ISSN | 1520-4804 |
Publisher | American Chemical Society |
Peer Reviewed | Peer Reviewed |
Volume | 59 |
Issue | 2 |
Pages | 721-732 |
DOI | https://doi.org/10.1021/acs.jmedchem.5b01771 |
Keywords | Molecular Medicine; Drug Discovery |
Public URL | https://nottingham-repository.worktribe.com/output/4842962 |
Publisher URL | https://pubs.acs.org/doi/10.1021/acs.jmedchem.5b01771 |
Additional Information | This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Medicinal Chemistry,copyright© American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://pubs.acs.org/doi/10.1021/acs.jmedchem.5b01771 |
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