A versatile study of novel A3B-type unsymmetric zinc(II) phthalocyanines containing thiazolidin-4-one: Their, carbonic anhydrase I, II isoenzymes, and xanthine oxidase inhibitors evaluation

Abstract

In this study, four novel phthalocyanine complexes containing zinc metal were synthesized. After preparing the starting compounds (2-(4-hydroxyphenyl)-3-phenylthiazolidin-4-one 1 and 2-(4-(2-hydroxyethoxy)phenyl)-3-phenylthiazolidin-4-one 3 by the conventional method, they were reacted with 4-nitrophthalonitrile separately using K2CO3 in DMF. Compounds 2 and 4, are well-documented compounds for obtaining phthalocyanines. Subsequently, synthesized phthalonitrile compounds 2 and 4 were reacted with Zn(II) salt at high temperature in the presence of DBU to convert them into targeted symmetrical (2a, 4a) and unsymmetrical (2b, 4b) phthalocyanines under suitable conditions. Their photochemical, photophysical, and electrochemical features were then examined. These metallophthalocyanines indicated good solubility in some organic solvents, such as DMSO, DMF, THF, DCM, and CHCl3. Furthermore, the structures of ligands (1, 2, 3, 4) were determined by 1H NMR, 13C NMR, and FT-IR spectrometry, while complexes (2a, 2b, 4a, 4b) were determined by FT-IR, UV–Vis, fluorescence, and MALDI-TOF spectrometry. Inhibitory effects of ligand and phthalocyanine compounds (1, 2, 3, 4, 2a, 2b, 4a, 4b) against human erythrocyte carbonic anhydrase I (hCA I) and II (hCA II) isoenzymes, as well as cow's milk xanthine oxidase (XO), were examined. It was found that 2a, 2b, 4a, and 4b had strong inhibition effects at micromolar levels against all three. The compounds 2b and 4b showed stronger inhibition effects for hCA I and II than 2a and 4a. In the case of XO, although the inhibition effects of these molecules (2b, 4a, 4b) were similar, 2a had the strongest inhibition effect. Since CA and XO inhibitors are the target molecules of drug development studies to be used in the treatment of many diseases, the results of this study will aid drug design studies in the development of new XO and CA inhibitors. © 2022 Elsevier B.V.