ANTIOXIDANT AND ANTICANCER PROPERTIES OF METALLO-SALENS

Abstract

Current anticancer agents do not greatly differentiate between normal cells and cancer cells. This leads to adverse effects and systemic toxicity, most of the drugs produce side effects in other tissues which limit the maximum allowable dose of drug. In an effort to find a novel metal complex that can be used in cancer therapy, a series of Mn(III) salen derivatives were synthesized and then characterized biochemically. A total of 18 compounds were tested on human neuroblastoma cells (SH-SY5Y) and immortalized mouse hippocampal cell line (HT22). Sixteen out of eighteen compounds showed cytotoxic effects towards human neuroblastoma cells (SH-SY5Y) at very low concentrations with IC50 values ranging from 1.5 to 76 µM. Fifteen out of eighteen compounds showed low cytotoxicity on HT22 cell line. The drugs were also screened in presence of ethanol which causes DNA damage and stops cells from repairing the damage. The drugs showed strong cytotoxicity towards SH-SY5Y in the presence of ethanol, surprisingly the same drugs showed least effects on the HT22 cells. In fact they rather promoted cell growth at higher concentrations. Nuclear fragmentation in the presence and absence of drug and ethanol was studied by staining cells with DAPI (4',6-diamino-2-phenylindole). Differential interference contrast (DIC) microscopy images were taken to check the cell morphology. These Mn(III) salen derivatives showed great specificity towards cancer cells and they are very effective at lower concentrations compared to most widely used anticancer drug Cisplatin.