The investigation of carbonic anhydrase and paraoxonase enzyme inhibition properties of water-soluble zinc and gallium phthalocyanine complexes (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 (CA) I and II isoenzymes and paraoxonase (PON1) 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 (off-target cytosolic isoforms) inhibitory activity (Ki values of 26.09 μM and 43.11 μM for hCA I and 30.95 μM and 33.19 μM for hCA II, respectively), they exhibited strong PON1 (associated with high-density lipoprotein [HDL]) inhibitory activity (Ki values of 0.37 μM and 0.27 μM, 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 more 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.
Phthalocyanine, sulfonated, water-soluble, paraoxonase, carbonic anhydrase, enzyme inhibition, molecular docking
GÜZEL, EMRE; SÖNMEZ, FATİH; ERKAN, SULTAN; ÇIKRIKCI, KÜBRA; ERGÜN, ADEM; GENÇER, NAHİT; ARSLAN, OKTAY; and KOÇAK, MAKBULE
"Evaluation of carbonic anhydrase and paraoxonase inhibition activities and molecular docking studies of highly water-soluble sulfonated phthalocyanines,"
Turkish Journal of Chemistry: Vol. 44:
6, Article 11.
Available at: https://journals.tubitak.gov.tr/chem/vol44/iss6/11