Anticancer investigation of platinum and copper-based complexes containing quinoxaline ligands

Abstract

This research focuses on synthesis and anticancer activity of trans-[(dichloro)bisdipyridlquinoxalino] and [(dichloro)bisdithienylquinoxalino]copper(II)/platinum(II) compounds as prodrug candidates. The binding interaction of these compounds with calf thymus DNA (CT-DNA) and human serum albumin (HSA) of the complexes were assessed with UV titration, thermal decomposition, viscometric, and fluorometric measurements. The nature of the binding of the complexes on DNA were revealed as electrostatic interaction between the cationic metal complexes ion and the negative phosphate groups of CT-DNA upon removal of the counter ion, chloride. In addition, our complexes induced a surface contact through the hydrophobic region of protein. Antitumor activity of the complexes against human glioblastoma A172, LN229, and U87 cell lines and human lung A549, human breast MDA-231, human cervix HeLa, and human prostate PC-3 cell lines were investigated by examining cell viability, oxidative stress, apoptosis, and migration/invasion. Cytotoxicity of the complexes was evaluated by MTT test. The U87 and HeLa cells were investigated as the cancer cells most sensitive to our complexes. The exerted cytotoxic effect of dipyridlquinoxalino and dithienylquinoxalino copper(II)/platinum(II) complexes was attributed to the formation of the reactive oxygen species in vitro. It is clearly demonstrated that trans-[(dichloro)bisdithenylquinoxalino]copper (II) (Cu(dtq)) has the highest DNA degradation potential and anticancer effect among the tested complexes by leading apoptosis. Wound healing and invasion analysis results also supported the anticancer activity of Cu(dtq).