Matthias Bache, Niels V Heise, Andreas Thiel, Anne Funtan, Franziska Seifert, Marina Petrenko, Antje Güttler, Sarah Brandt, Thomas Mueller, Dirk Vordermark, Iris Thondorf, René Csuk, Reinhard Paschke
Human carbonic anhydrase IX (hCA IX) is a zinc(II)-dependent metalloenzyme that plays a critical role in the conversion of carbon dioxide and water to protons and bicarbonate. It is a membrane-bound protein with an extracellular catalytic center that is predominantly overexpressed in solid hypoxic tumors. Sulfamates and sulfonamides, for example acetazolamide (AZA), have been used to inhibit hCA IX in order to improve the response to solid hypoxic tumors. In the present study, we propose a new drug targeting approach by attaching the natural cytotoxic substances betulin and betulinic acid (BA) via a linker to sulfonamides...
March 14, 2024: Pharmaceutics