Synthesis of 3,4-dihydroxypyrrolidine-2,5-dione and 3,5-dihydroxybenzoic acid derivatives and evaluation of the carbonic anhydrase I and II inhibition.
The inhibition of two human cytosolic carbonic anhydrase (hCA, EC 4.2.1.1) isozymes I and II, with some 3,4-dihydroxypyrrolidine-2,5-dione and 3,5-dihydroxybenzoic acid derivatives, were investigated by using the esterase assay, with 4-nitrophenyl acetate (4-NPA) as substrate. Compounds 10-13 showed KI values in the range of 112.7-441.5 μM for hCA I and of 3.5-10.76 μM against hCA II, respectively. These hydroxyl group containing compounds generally were competitive inhibitors. Some hydroxyl group containing compounds investigated here showed effective hCA II inhibitory effects, in the same range as the clinically used sulfonamide acetazolamide, and might be used as leads for generating enzyme inhibitors possibly targeting other CA isoforms which have not been yet assayed for their interactions with such agents.
a Engineering Faculty, Department of Polymer Engineering , Yalova University , Yalova , Turkey .|b Science and Art Faculty, Chemistry Department , Fatih University , Istanbul , Turkey .
Mehmet
M
Arslan
c Science and Art Faculty, Chemistry Department , Ağri İbrahim Çeçen University , Ağri , Turkey .
Murat
M
Şentürk
d Chemistry Department , Gebze Institute of Technology , Kocaeli , Turkey .
İsmail
İ
Fidan
e Department of Chemistry , Karamanoğlu Mehmetbey University , Karaman , Turkey .
Oktay
O
Talaz
f Faculty of Agriculture , Department of Agricultural Biotechnology, Ondokuz Mayıs University , Samsun , Turkey , and.
Deniz
D
Ekinci
b Science and Art Faculty, Chemistry Department , Fatih University , Istanbul , Turkey .
Sedat
S
Coşgun
g Polo Scientifico, Laboratorio di Chimica Bioinorganica , Università degli Studi di Firenze , Sesto Fiorentino , Florence , Italy.
Claudiu T
CT
Supuran
D024401:Carbonic Anhydrase I / Q000037:antagonists & inhibitors* / Q000302:isolation & purification / Q000378:metabolism; D024402:Carbonic Anhydrase II / Q000037:antagonists & inhibitors* / Q000302:isolation & purification / Q000378:metabolism; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D062385:Hydroxybenzoates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015394:Molecular Structure; D012118:Resorcinols / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013388:Succinimides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D002257:Carbonic Anhydrase Inhibitors; D062385:Hydroxybenzoates; D012118:Resorcinols; D013388:Succinimides; C076950:alpha-resorcylic acid; D024401:Carbonic Anhydrase I; D024402:Carbonic Anhydrase II
Benzoic acid; carbonic anhydrase; enzyme inhibitor; hydroxyl; pyrrolidine