title: Synthesis and carbonic anhydrase inhibitory properties of amino acid - coumarin/quinolinone conjugates incorporating glycine, alanine and phenylalanine moieties.
abstract: N-Protected amino acids (Gly, Ala and Phe) were reacted with amino substituted coumarin and quinolinone derivatives, leading to the corresponding N-protected amino acid-coumarin/quinolinone conjugates. The carbonic anhydrase (CA, EC 4.2.1.1) inhibitory activity of the new compounds was assessed against various human (h) isoforms, such as hCA I, hCA II, hCA IV and hCA XII. The quinolinone conjugates were inactive as enzyme inhibitors, whereas the coumarins were ineffective hCA I/II inhibitors (KIs > 50 μM) but were submicromolar hCA IV and XII inhibitors, with inhibition constants ranging between 92 nM and 1.19 μM for hCA IV, and between 0.11 and 0.79 μM for hCA XII. These coumarin derivatives, as many others reported earlier, thus show an interesting selective inhibitory profile for the membrane-bound over the cytosolic CA isoforms.
authors.affiliation: a Department of Basic Pharmaceutical Sciences , Faculty of Pharmacy, İnönü University , Malatya , Turkey .|b Laboratorio Di Chimica Bioinorganica E Dipartimento Neurofarba , Sezione Di Scienze Farmaceutiche E Nutraceutiche, Università Degli Studi Di Firenze , Sesto Fiorentino , Florence , Italy , and.
authors.forename: F Zehra
authors.initials: FZ
authors.lastname: Küçükbay
authors.affiliation: b Laboratorio Di Chimica Bioinorganica E Dipartimento Neurofarba , Sezione Di Scienze Farmaceutiche E Nutraceutiche, Università Degli Studi Di Firenze , Sesto Fiorentino , Florence , Italy , and.|c Department of Chemistry , Faculty of Arts and Science, İnönü University , Malatya , Turkey.
authors.forename: Hasan
authors.initials: H
authors.lastname: Küçükbay
authors.affiliation: b Laboratorio Di Chimica Bioinorganica E Dipartimento Neurofarba , Sezione Di Scienze Farmaceutiche E Nutraceutiche, Università Degli Studi Di Firenze , Sesto Fiorentino , Florence , Italy , and.
authors.forename: Muhammet
authors.initials: M
authors.lastname: Tanc
authors.affiliation: b Laboratorio Di Chimica Bioinorganica E Dipartimento Neurofarba , Sezione Di Scienze Farmaceutiche E Nutraceutiche, Università Degli Studi Di Firenze , Sesto Fiorentino , Florence , Italy , and.
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D000409:Alanine / Q000737:chemistry*; D000596:Amino Acids / Q000737:chemistry / Q000494:pharmacology*; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000187:drug effects*; D003374:Coumarins / Q000737:chemistry*; D005998:Glycine / Q000737:chemistry*; D010649:Phenylalanine / Q000737:chemistry*; D015363:Quinolones / Q000737:chemistry*
chemical_list: D000596:Amino Acids; D002257:Carbonic Anhydrase Inhibitors; D003374:Coumarins; D015363:Quinolones; D010649:Phenylalanine; C030123:coumarin; D002256:Carbonic Anhydrases; D000409:Alanine; D005998:Glycine
keywords: Carbonic anhydrase; N-protected amino acid derivatives; coumarin; inhibitor