title: Synthesis and carbonic anhydrase I, II, IV and XII inhibitory properties of N-protected amino acid - sulfonamide conjugates.
abstract: N-protected amino acids (Gly, Ala and Phe protected with Boc and Z groups) were reacted with sulfonamide derivatives, leading to the corresponding N-protected amino acid-sulfonamide conjugates. The carbonic anhydrase (CA, EC 4.2.1.1) inhibitory activity of the new compounds was assessed against four human (h) isoforms, hCA I, hCA II, hCA IV and hCA XII. Among them, hCA II, IV and XII are antiglaucoma drug targets, being involved in aqueous humor secretion within the eye. Low nanomolar inhibition was measured against all four isoforms with the 20 reported sulfonamides, but no selective inhibitory profiles, except for some CA XII-selective derivatives, were observed. hCA I, II and XII were generally better inhibited by sulfonamides incorporating longer scaffolds and Gly/Ala, whereas the best hCA IV inhibitors were homosulfanilamide derivatives, incorporating Phe moieties. The amino acid-sulfonamide conjugates show good water solubility and effective hCA II, IV and XII inhibition, and may be considered as interesting candidates for antiglaucoma studies.
authors.affiliation: a Department of Basic Pharmaceutical Sciences , Faculty of Pharmacy, İnönü University , Malatya , Turkey .|b Dipartimento Neurofarba, Sezione Di Scienze Farmaceutiche E Nutraceutiche e Laboratorio Di Chimica Bioinorganica, Università Degli Studi Di Firenze , Sesto Fiorentino , Florence , Italy , and.
authors.forename: F Zehra
authors.initials: FZ
authors.lastname: Küçükbay
authors.affiliation: b Dipartimento Neurofarba, Sezione Di Scienze Farmaceutiche E Nutraceutiche e Laboratorio Di Chimica Bioinorganica, 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 Dipartimento Neurofarba, Sezione Di Scienze Farmaceutiche E Nutraceutiche e Laboratorio Di Chimica Bioinorganica, Università Degli Studi Di Firenze , Sesto Fiorentino , Florence , Italy , and.
authors.forename: Muhammet
authors.initials: M
authors.lastname: Tanc
authors.affiliation: b Dipartimento Neurofarba, Sezione Di Scienze Farmaceutiche E Nutraceutiche e Laboratorio Di Chimica Bioinorganica, Università Degli Studi Di Firenze , Sesto Fiorentino , Florence , Italy , and.
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D000596:Amino Acids / Q000737:chemistry* / Q000494:pharmacology*; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000187:drug effects*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D013057:Spectrum Analysis / Q000379:methods; D013449:Sulfonamides / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000596:Amino Acids; D002257:Carbonic Anhydrase Inhibitors; D007527:Isoenzymes; D013449:Sulfonamides; D002256:Carbonic Anhydrases
keywords: Carbonic anhydrase; N-protected amino acid; glaucoma; inhibitor; sulfonamide