Looking toward the Rim of the Active Site Cavity of Druggable Human Carbonic Anhydrase Isoforms(45 views visite) Mancuso F, Di Fiore A, De Luca L, Angeli A, Monti SM, De Simone G, Supuran CT, Gitto R
Acs Med Chem Lett (ISSN: 1948-5875linking), 2020 May 14; 11(5): 1000-1005.
Keywords Parole chiave: Not available. Non disponibili.
Affiliations Affiliazioni: *** IBB - CNR ***
Dipartimento di Scienze Chimiche, Biologiche, Farmaceutiche ed Ambientali (CHIBIOFARAM), Università degli Studi di Messina, Viale Palatucci, Polo Didattico SS. Annunziata, 98168 Messina, Italy.
Istituto di Biostrutture e Bioimmagini-CNR, Via Mezzocannone 16, 80134 Napoli, Italy.
Dipartimento NEUROFARBA, Università di Firenze, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Italy.
References Riferimenti: Not available. Non disponibili.
Looking toward the Rim of the Active Site Cavity of Druggable Human Carbonic Anhydrase Isoforms
We report the synthesis and biochemical evaluation of a series of substituted 4-(4-aroylpiperazine-1-carbonyl)benzenesulfonamides (5a-s) developed as inhibitors of druggable carbonic anhydrase (CA) isoforms, as tools for the identification of new therapeutics. X-ray crystallography confirmed that this class of benzenesulfonamides binds CAs through the canonical anchoring of the benzenesulfonamide moiety to the metal ion and a tail-mediated recognition of the middle/top area of the active site cavity. Compound 5e (R = 2-Cl) demonstrated relevant selectivity toward brain-expressed hCA VII. The best balancing in binding affinity and selectivity toward tumor-expressed hCA IX/hCA XII over ubiquitous hCA I/hCA II was found for inhibitor 5o (R = 3-NO(2)). Notably 5b (R = 2-F) proved to be the most efficacious inhibitor of hCA XII for which computational studies elucidated the CA recognition process.
Looking toward the Rim of the Active Site Cavity of Druggable Human Carbonic Anhydrase Isoforms
305 Records (281 escludendo Abstract e Conferenze). Impact factor totale: 1203.737 (1131.679 escludendo Abstract e Conferenze). Impact factor a 5 anni totale: 1172.715 (1089.815 escludendo Abstract e Conferenze).
Last modified by Ultima modifica di Gennaro Angrisano on in data Wednesday 13 January 2021, 14:37:33 45 views visite. Last view on Ultima visita in data Thursday 04 February 2021, 2:04:50