Synthesis, Characterization, in Vitro Cytotoxicity of Novel Metallo Phthalocyanines with Four Methylpropiophenonyl Clusters and Their Effects on Caenorhabditis Elegans Thermotolerance

Abstract

Phthalocyanines (Pcs) have the potential to be used in many medical applications. We synthesized novel 2-Hydroxy-4'-[2-hydroxyethoxy)]-2-methylpropiophenone substituted zinc (II), cobalt (II), and copper (II) Pcs by using 2-Hydroxy-4'-[2-(3,4-dicyanophenoxyethoxy)]-2-methylpropiophenone with metal salts in N, N-Dimethylformamide. New phthalonitrile ligand was prepared from 2-Hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone and 4-nitrophthalonitrile in N, N-Dimethylformamide (DMF) at 50 0 C using potassium carbonate as a catalyst. The compounds were characterized by elemental analysis, IR (Infrared spectroscopy), UV-Visible spectroscopy, and Laser Desorption ionization time-of-flight mass spectroscopic (LDI-TOF-MS) methods. The characteristics like toxicity and biological activities of the candidate drug are critical at the preclinical stages of development. In vitro and in vivo experimental models are employed in the discovery of a compound's nature. The cytotoxicity is measured on human cells, and with the use of nematode Caenorhabditis elegans (C. elegans), effects on life span are examined. Standard MTT assays were carried out using HeLa and L929 cells for cytotoxicity testing. Results showed that there was no significant decrease in the cell viability with zinc (II), cobalt (II), and copper (II) phthalocyanines (ZnPc, CoPc, and CuPc) at 0.25 μM concentration. C. elegans survival assay of ZnPc, CoPc, and CuPc under heat stress showed that although a dose-dependent statistically significant toxicity was observed for ZnPc and CuPc, CoPc was not toxic at all concentrations tested. CoPc even increased the survival of worms at the 1.36x10-1 µM concentration tested.