Next-generation polyamine human carbonic anhydrase inhibitors

Polyamines as small aliphatic molecules having multiple nitrogen atoms are widely present in all the organisms, including bacteria, archaea, fungi and the eukaryotic cells. Herein we review the class of polyamines as inhibitors of the catalytically active α-carbonic anhydrases (CAs; EC 4.2.1.1). The polyamines binding mode was investigated through crystallographic and kinetic experiments. The crystal structure of the spermine in adduct with the human (h) isoform hCA II is discussed in detail, as it proved a new inhibition mechanism with a novel class of CA inhibitors.