Küçükbay F Zehra, Küçükbay Hasan, Tanc Muhammet, Supuran Claudiu T
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.
J Enzyme Inhib Med Chem. 2016 Dec;31(6):1476-83. doi: 10.3109/14756366.2016.1147438. Epub 2016 Feb 21.
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.
N-保护氨基酸（用Boc和Z基团保护的甘氨酸、丙氨酸和苯丙氨酸）与磺酰胺衍生物反应，生成相应的N-保护氨基酸-磺酰胺缀合物。评估了新化合物对四种人类（h）同工型，即hCA I、hCA II、hCA IV和hCA XII的碳酸酐酶（CA，EC 4.2.1.1）抑制活性。其中，hCA II、IV和XII是抗青光眼药物靶点，参与眼内房水分泌。用20种报道的磺酰胺对所有四种同工型均测得低纳摩尔抑制率，但除了一些CA XII选择性衍生物外，未观察到选择性抑制谱。hCA I、II和XII通常被含有较长支架和甘氨酸/丙氨酸的磺酰胺更好地抑制，而最好的hCA IV抑制剂是含有苯丙氨酸部分的同型磺胺衍生物。氨基酸-磺酰胺缀合物显示出良好的水溶性和对hCA II、IV和XII的有效抑制作用，可被视为抗青光眼研究的有趣候选物。
