Evaluation of carbonic anhydrase and paraoxonase inhibition activities and molecular docking studies of highly water-soluble sulfonated phthalocyanines

Authors : Emre GUZEL, Fatih SONMEZ, Sultan ERKAN, Kubra CİKRİKCİ, Adem ERGUN, Nahit GENCER, Oktay ARSLAN, Makbule B. KOCAK

Pages : 1565-1573

View : 19 | Download : 6

Publication Date : 0000-00-00

Article Type : Research Paper

Abstract :The investigation of carbonic anhydrase and paraoxonase enzyme inhibition properties of water-soluble zinc and gallium phthalocyanine complexes insert ignore into journalissuearticles values(1 and 2); are reported for the first time. The binding of p-sulfonylphenoxy moieties to the phthalocyanine structure favors excellent solubilities in water, as well as providing an inhibition effect on carbonic anhydrase insert ignore into journalissuearticles values(CA); I and II isoenzymes and paraoxonase insert ignore into journalissuearticles values(PON I); enzyme. According to biological activity results, both complexes inhibited hCA I, hCA II, and PON1. Whereas 1 and 2 showed moderate hCA I and hCA II insert ignore into journalissuearticles values(off-target cytosolic isoforms); inhibitory activity insert ignore into journalissuearticles values(K-i values of 26.09 mu M and 43.11 mu M for hCA I and 30.95 mu M and 33.19 mu M for hCA II, respectively);, they exhibited strong PON1 insert ignore into journalissuearticles values(associated with high-density lipoprotein [HDL]); inhibitory activity insert ignore into journalissuearticles values(K-i values of 0.37 mu M and 0.27 mu M, respectively);. The inhibition kinetics were analyzed by Lineweaver-Burk double reciprocal plots. It revealed that 1 and 2 were noncompetitive inhibitors against PON1, hCA I, and hCA II. These complexes can be snore advantageous than other synthetic CA and PON inhibitors due to their water solubility. Docking studies were carried out to examine the interactions between hCA I, hCA II, and PON1 inhibitors and metal complexes at a molecular level and to predict binding energies.
Keywords : Phthalocyanine, sulfonated, water soluble, paraoxonase, carbonic anhydrase, enzyme inhibition, molecular docking