Rationally designed copper-deferiprone-phenanthroline complex as a dual anticancer and SARS-CoV-2 inhibitor.

A novel ternary copper-deferiprone-phenanthroline complex was rationally designed, synthesized, and thoroughly characterized. DNA interaction studies revealed that deferiprone binds to CT-DNA via groove binding, whereas the copper complex predominantly intercalates. The complex exhibited remarkable cytotoxicity against HT-29, HepG2, and MDA-MB-468 human cancer cell lines, while showing lower toxicity toward normal HEK-293 cells. Compared to cisplatin, doxorubicin, oxaliplatin, fluorouracil, and deferiprone, the copper complex demonstrated significantly enhanced anticancer potency. Flow cytometry analysis indicated late-stage apoptosis induction and G1-phase cell cycle arrest. Gene expression studies showed down-regulation of BCL2 and up-regulation of BAX, Caspase-3, and the BAX/BCL2 ratio, confirming apoptosis-mediated cytotoxicity. In addition, molecular docking revealed strong binding affinities of the complex toward key SARS-CoV-2 targets, including the main protease (Mpro), papain-like protease (PLpro), nucleocapsid N-terminal RNA-binding domain, and RNA-dependent RNA polymerase (RdRp), surpassing several currently available antiviral agents. Collectively, these findings identify the copper-deferiprone-phenanthroline complex as a promising candidate for dual biomedical applications, serving as both an anticancer agent and a potential SARS-CoV-2 inhibitor.