A new series of chiral thiourea derivatives (5a-5c) and thiourea containing benzimidazole moieties (9b-9e) were synthesized from different amino acids (l-valine, l-isoleucine, l-methionine, l-phenylalanine, and d-phenylglycine). The compounds were characterized and tested against the two most studied members of the pH regulatory enzyme family, carbonic anhydrase (CA, EC 4.2.1.1). KI values of the novel compounds were measured in the range of 3.4-73.6 μM for hCA I isozyme and 8.7-1.44.2 μM for hCA II isozyme, respectively. Phenol was also tested as standard in order to understand the structure activity relationship and the clinically used sulfonamide acetazolamide was tested for comparison reasons. All of the compounds exhibited competitive inhibition with 4-nitrophenylacetate as substrate.
Keywords: Amino acid; benzimidazole; biological activity; carbonic anhydrase; thiourea.