Synthesis of water soluble tetra-substituted phthalocyanines: Investigation of DNA cleavage, cytotoxic effects and metabolic enzymes inhibition

Abstract

In this study, we have reported the synthesis and characterization of 4-(sodium 2-mercaptoethane sulfonate) phthalonitrile (1) as ligand and its water-soluble phthalocyanine compounds [M = 2H (2), Zn(II) (3), Ga(III)Cl (4), In(III)Cl (5)] containing sodium 2-mercaptoethanesulfonate substituents at the peripheral positions. All compounds were characterized by UV-Vis, FT-IR and NMR spectroscopies, and MALDI-TOF mass spectra. Besides, the DNA cleavage effects of the phthalocyanine compounds were investigated using agarose gel electrophoresis and cytotoxic effects of them were determined on BT-20, DU-145, A549, SNU-398 and HFC cell lines using MTT assay. The compounds cleaved supercoiled pBR322 plasmid DNA upon irradiation (white, 17.5 mW/cm(2), 60 min) in the presence of H2O2. The IC50 values of (2) were determined as 145.76, 93.75, 124.73, 128.81 and 136 mM on BT-20, DU-145, A549, SNU-398 and HFC cell lines, respectively. The IC50 values of others were above 200 mM on five cell lines. These results showed that the compounds had low cytotoxic effects against breast, prostate, lung and liver cell lines. These water-soluble phthalocyanine compounds [M = 2H (2), Zn(II) (3), Ga(III)Cl (4), In(III)Cl (5)] were found to be good inhibitor against the alpha-glycosidase, human carbonic anhydrase I and II isoforms, and both cholinesterase enzymes with Ki values in the range of 84.02 +/- 16.95-166.47 +/- 14.87 mM for alpha-glycosidase, 7.54 +/- 1.02-31.65 +/- 3.08 mM for hCA I, 5.97 +/- 0.97-36.13 +/- 6.97 mM for hCA II, 1.02 +/- 0.14-3.42 +/- 0.86 mM for BChE, and 2.01 +/- 0.32-3.98 +/- 0.12 mM for AChE, respectively. (C) 2020 Elsevier B.V. All rights reserved.