jm6b00616_si_001.pdf (242.4 kB)

1,2-Benzisothiazole Derivatives Bearing 4‑, 5‑, or 6‑Alkyl/arylcarboxamide Moieties Inhibit Carbonic Anhydrase Isoform IX (CAIX) and Cell Proliferation under Hypoxic Conditions

Download (242.4 kB)
journal contribution
posted on 15.06.2016, 00:00 by Vito Coviello, Beatrice Marchi, Stefania Sartini, Luca Quattrini, Anna Maria Marini, Francesca Simorini, Sabrina Taliani, Silvia Salerno, Paola Orlandi, Anna Fioravanti, Teresa Di Desidero, Daniela Vullo, Federico Da Settimo, Claudiu T. Supuran, Guido Bocci, Concettina La Motta
Three novel series of 1,2-benzisothiazole derivatives have been developed as inhibitors of carbonic anhydrase isoform IX. Compounds 5c and 5j, tested in vitro on the human colon cell line HT-29, blocked the growth of cells cultured under chemically induced hypoxic conditions, displaying a specific activity against cancer cells characterized by CAIX up-regulation. Moreover, a synergistic activity of 5c with SN-38 (the active metabolite of irinotecan) and 5-fluorouracil on cell proliferation under hypoxic conditions was demonstrated.