Synthesis and biological evaluation of new silicon(IV) phthalocyanines as carbonic anhydrase and cholinesterase inhibitors

Abstract

In this study, novel silicon(IV)phthalocyanines (SiPcs) containing 4-hydroxypyridine (1a), N-(2-hydroxyethyl)succinimide (2a) and N-(2-hydroxyethyl)phthalimide (3a) at their axial positions were synthesized for the first time and surveyed in vitro for key molecular targets. Characterization of new compounds was validated using various spectroscopy techniques. The inhibitory activities of axially disubstituted silicon phthalocyanines were also investigated against carbonic anhydrase isoforms hCA I, II (cytosolic, ubiquitous isozymes), and IX (transmembrane, cancerassociated isozyme) and cholinesterases (AChE and BChE, which are associated with Alzheimer’s disease). Against these five esterase enzymes, all synthesized molecules indicated great inhibition effects with IC50 values in the range of 49.51–231.05 nM. Among the three silicon(IV)phthalocyanines, 3a showed most potent inhibitory activity towards both hCA I, AChE and BChE. 1a demonstrated also the most effective inhibition for hCA II and hCA IX. This work is also the first example of cancer-associated isozyme hCA IX inhibition by silicon(IV)phthalocyanines.