Synthesis, carbonic anhydrase inhibition studies and modelling investigations of phthalimide-hydantoin hybrids.

A novel series of hydantoins incorporating phthalimides has been synthesised by condensation of activated phthalimides with 1-aminohydantoin and investigated for their inhibitory activity against a panel of human (h) carbonic anhydrase (CA, EC 4.2.1.1): the cytosolic isoforms hCA I, hCA II, and hCA VII, secreted isoform hCA VI, and the transmembrane hCA IX, by a stopped-flow CO 2 hydrase assay. Although all newly developed compounds were totally inactive on hCA I and mainly ineffective towards hCA II, they generally exhibited moderate repressing effects on hCA VI, VII, and IX with K I s values in the submicromolar to micromolar ranges. The salts 3a and 3b , followed by derivative 5 , displayed the best inhibitory activity of all the evaluated compounds and their binding mode was proposed in silico . These compounds can also be considered interesting starting points for the development of novel pharmacophores for this class of enzyme inhibitors.