Cytotoxic activity against neuroblastoma and mouse fibroblast cell lines, in silico molecular modeling studies and enzyme activity of axial silicon, both peripheral and non-peripheral zinc phthalocyanines

Abstract

The cytotoxic effects of axial disubstituted silicon phthalocyanine (SiPc) and both peripheral and non-peripheral substituted zinc phthalocyanines (ZnPcp/np) were evaluated on neuroblastoma (SH-SY5Y) and mouse fibroblast (NIH-3T3) cell lines utilizing the MTT assay. All evaluated drugs had a pronounced cytotoxic impact on SH-SY5Y cells, with IC50 values much lower than those observed in NIH-3T3 cells, which displayed the highest IC50 values. These results imply that produced phthalocyanines (SiPc, ZnPcp/np) may be effective, specific, and promising therapeutic candidates for the treatment of neuroblastoma. In addition, the activities of these compounds (SiPc, ZnPcp/np) on alpha-glucosidase and hCA I and II isozymes, which were developed as inhibitors in the treatment of diseases such as diabetes, cancer, glaucoma, obesity, and epilepsy, were also determined. The results obtained proved that these compounds (SiPc, ZnPcp/np) were more potent alpha-glucosidase inhibitors than Acarbose (IC50: 4.58 mu M), which was used as a positive control. Molecular docking calculations of dinitrile derivatives (CNp/np), which are precursor molecules for phthalocyanines, and metal complexes (SiPc, ZnPcp/np) were performed on a series of proteins, including hCA I enzyme protein (PDB ID: 2CAB), hCA II enzyme protein (PDB ID: 3DC3), alpha-Gly enzyme protein (PDB ID: 1UAS), and SH-SY5Y cell protein (PDB ID: 3PBL, 7CKZ, and 7LQZ).