Investigation on the Cytotoxicity of Hydroxycinnamic and Hydroxybenzoic Acid-Based Natural Antioxidant Conjugated...

Higher intracellular ROS concentration of TNBC cells may serve as a therapeutic target to develop antioxidant-based drugs to treat such cancers. The HCA-conjugated terpyridine-copper analogues are reported for the selective treatment of TNBC, but the investigation on the antiproliferative activities remains to be elucidated. Herein, a set of terpyridine-conjugated HBA and HCA derivatives and their ROS-induced products were isolated and evaluated for their anti-TNBC properties. In vitro studies on 4T1 cell lines revealed that the ROS-oxidized intermediates showed potential therapeutic activity to cause the antiproliferative activity of their parent analogues. Further, the presence of copper was also found to enhance the anticancer activity of these derivatives with high selectivity toward TNBC. Due to the presence of natural antioxidant residues, all these derivatives were found to be biocompatible, as studied over NIH/3T3 cell lines. These results illustrate the involvement of ROS-generated cytotoxic intermediates, responsible for the therapeutic applicability of natural antioxidant-based derivatives toward TNBC.