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4-Arylbenzenesulfonamides as Human Carbonic Anhydrase Inhibitors (hCAIs): Synthesis by Pd Nanocatalyst-Mediated Suzuki–Miyaura Reaction, Enzyme Inhibition, and X-ray Crystallographic Studies

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.
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https://hal.univ-reims.fr/hal-02436454
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Submitted on : Monday, January 13, 2020 - 9:47:26 AM
Last modification on : Wednesday, April 15, 2020 - 9:56:12 AM

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Benedetta Cornelio, Marie Laronze-Cochard, Mariangela Ceruso, Marta Ferraroni, Graham Rance, et al.. 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, American Chemical Society, 2016, 59 (2), pp.721-732. ⟨10.1021/acs.jmedchem.5b01771⟩. ⟨hal-02436454⟩

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