Design, Synthesis, Characterization of Peripherally Tetra Pyridine-Triazole Substituted Phthalocyanines and Their Inhibitor Effects on Cholinesterases (AChE/BChE) and Carbonic Anhydrases (hCA I, II and IX)
In this study, phthalocyanine precursors (5 and 9) and 1,2,3-triazole substituted metal-free and metallo phthalocyanines (9a-c) were designed, synthesized for the first time and evaluated in vitro on key molecular targets. The structure of novel compounds were characterized by FT-IR, 1H / 13C NMR, UV-Vis, Mass analysis. The compounds’ inhibitory activities were tested against human carbonic anhydrase isoforms hCA I, II (cytosolic, ubiquitous isozymes), IX (transmembrane, cancer-associated isozyme) and cholinesterases (AChE and BChE, which enzymes associated with Alzheimer). Among the three phthalocyanines and starting compounds, 9b showed the most interesting profile as a nanomolar selective inhibitor of hCA I (Ki=37.2 nM) and 9c showed the most effective inhibitor of hCA II, IX, AChE and BChE (Ki =41.9, 27.4, 5.8 and 45.8 nM, respectively). This study is also the first example of cancer-associated isozyme hCA IX inhibition of phthalocyanines.