Highly water soluble metallophthalocyanines and investigation of their AChE/BuChE enzyme inhibition and cytotoxic activity against human neuroblastoma (SH-SY5Y) cell

Abstract

The new morpholine substituted Mn(III), Co(II), Cu(II) and Zn(II) phthalocyanines compounds were synthesized for the first time by cyclotetramerization reaction. In addition, their water-soluble derivatives were obtained using a simple method, stirring CH₃I in chloroform at room temperature in the dark. The water-soluble compounds are highly soluble in water at room temperature. The inhibitory activities of these compounds against the cholinergic enzyme AChE/BuChE were investigated using a spectrophotometric method. When compared to the positive control galantamine, all of the water-soluble phthalocyanine compounds demonstrated strong inhibition of AChE/BuChE with values of 4.51 µM and 7.37 µM, respectively. MT-C3-ZnQ had the highest inhibition activity of the compounds tested. Kinetic studies were performed in a systematic manner to determine the type of inhibition and the inhibitor’s binding constant to the enzyme. As a result, it was discovered that compound MT-C3-ZnQ inhibited AChE/BuChEs of mixed type. Furthermore, the cell viability of the MT-C3-ZnQ compound on the human neuroblastoma (SH-SY5Y) cell line was assessed at 24 and 48 h using the MTT assay. The MTT assay revealed that SH-SY5Y cells exposed to MT-C3-ZnQ for 24 h exhibited no cytotoxicity, with no apparent dose–response relationship. Similarly, no cytotoxicity was observed after 48 h of exposure and cell viability above 70 % was observed, compared to the control group. All of these findings suggest that the MT-C3-ZnQ compound, with its low cytotoxicity and high enzyme inhibition activity against AChE/BuChE enzymes, could be a viable alternative to drugs used in the treatment of Alzheimer’s. Furthermore, this study is expected to serve as a model for future research in this area.