Lupane acetates in small molecule drug hybrids: Probing their inhibitory activity for carbonic anhydrase II

Earlier studies had shown the potential of modified pentacyclic triterpenes as possible inhibitors of carbonic anhydrase II (CA II). In an extension of our earlier studies, betulin, betulinic acid and, for comparison purposes, glycyrrhetinic acid, ursolic acid and oleanolic acid were therefore converted into the respective acetates and linked to either taurinamide or de-acetylated acetazolamide via a variable linker. In particular, the derivatives 8 and 18 derived from betulinic acid or betulin and provided with a long spacer were found to be strong competitive inhibitors of CA II, thereby holding K_i = 1.27 and 0.20 μM, respectively.