title: Synthesis and biological activity of novel thiourea derivatives as carbonic anhydrase inhibitors.
abstract: 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.
authors.affiliation: Department of Chemistry, Science Faculty, Ege University , Izmir , Turkey .
authors.forename: Neslihan
authors.initials: N
authors.lastname: Korkmaz
authors.forename: Oday A
authors.initials: OA
authors.lastname: Obaidi
authors.forename: Murat
authors.initials: M
authors.lastname: Senturk
authors.forename: Demet
authors.initials: D
authors.lastname: Astley
authors.forename: Deniz
authors.initials: D
authors.lastname: Ekinci
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D000086:Acetazolamide / Q000737:chemistry; D000596:Amino Acids / Q000737:chemistry*; D001562:Benzimidazoles / Q000737:chemistry*; D024401:Carbonic Anhydrase I / Q000737:chemistry*; D024402:Carbonic Anhydrase II / Q000737:chemistry*; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry*; D057075:Enzyme Assays; D006801:Humans; D007700:Kinetics; D009596:Nitrophenols / Q000737:chemistry; D019800:Phenol / Q000737:chemistry; D011994:Recombinant Proteins / Q000737:chemistry; D013329:Structure-Activity Relationship; D013890:Thiourea / Q000031:analogs & derivatives* / Q000138:chemical synthesis
chemical_list: D000596:Amino Acids; D001562:Benzimidazoles; D002257:Carbonic Anhydrase Inhibitors; D009596:Nitrophenols; D011994:Recombinant Proteins; D019800:Phenol; C008642:4-nitrophenyl acetate; D024401:Carbonic Anhydrase I; D024402:Carbonic Anhydrase II; D013890:Thiourea; D000086:Acetazolamide
keywords: Amino acid; benzimidazole; biological activity; carbonic anhydrase; thiourea