ANTIOXIDATIVE AND ANTINEOPLASTIC EFFECTS OF Mn(III) SALPHENS, S-ALLYL CYSTEINE AND ITS SYNTHETIC ANALOGUES

Abstract

Presently used chemotherapeutic drugs are not very selective and do not have the capability to differentiate between normal cells and malignant cells, which leads to the development of adverse side-effects and systemic toxicity. The primary goal of this study is to discover a novel drug which can be used in the treatment of cancer as a chemotherapeutic drug. Here we have synthesized and screened 14 different compounds (12 metallo-salen complexes and 2 amino acid based compounds) and evaluated their cytotoxicity on human neuroblastoma cell line (SH-SY5Y) and mouse hippocampal cell line (HT22). Out of the 12 metal-complexes, 5 complexes had a better cytotoxic effect on the neuroblastoma cell line with IC₅₀ value in the range 1.5 - 64 μM in SH-SY5Y cell line. 9 out of the 12 metallo-complexes showed low cytotoxicity towards the hippocampal cell line HT22. The same set of metallo-salen complexes and amino acid derivatives (S-allyl cysteine (SAC) and its derivative S-benzyl cysteine (SBC)) were screened for their antioxidant activities in HT22 cells using an ethanol-induced oxidative stress based antioxidant assay. These analysis demonstrated that several metallo-salens, SAC and SBC showed protective effects in HT22 cells in the presence of ethanol. The compounds 3,3’-dihydroxy Mn(III) salphen (5) and 4,4’-dimethoxy Mn(III) salphen (9) also showed inhibition of colony formation in the case of SH-SY5Y cell line, with the compound 9 being the most effective. Overall, our studies demonstrate novel cytotoxic and neuroprotective effects of metallo-salen derivatives, SAC and SBC.