CU-01

Breast cancer ranks first among female malignant tumors and is the largest cancer worldwide. Recently, research on chiral metal-based complexes for cancer treatment has significantly increased. This study synthesized an L-copper(II) complex Cu-1 and a pair of chiral nickel(II) complexes Ni-1 (L-type) and Ni-2 (D-type). The antiproliferative activities of Cu-1, Ni-1, and Ni-2 against female malignant tumor cells (MCF-7, MDA-MB-231, SKOV3, Hela) were evaluated. Among them, the L-type complexes Cu-1 and Ni-1 exhibited superior bioactivity compared to the D-type Ni-2. Further mechanistic studies demonstrated that Cu-1 and Ni-1 could effectively inhibit the growth of MCF-7 cells. Additionally, in vivo experiments in nude mice verified that Cu-1 could exert anti-tumor effects through the synergistic action of multiple pathways. In summary, Cu-1 and Ni-1 possess multiple functions including anti-tumor angiogenesis, anti-inflammatory, apoptosis, and copper-induced death, providing theoretical reference for the development of breast cancer drugs.

In recent years, the pace of novel antibiotic development has been relatively slow, intensifying the urgency of the antibiotic resistance issue. Consequently, scientists have turned their attention to enhancing antibiotic activity by coordinating antibiotics with metal elements. This study designs and synthesizes three novel antibacterial copper complexes based on Gatifloxacin. These complexes exhibit potent antibacterial activity, notably Cu-1, with a minimum inhibitory concentration (MIC) of only 0.063 μg/mL against Staphylococcus aureus (S.aureus), demonstrating potent bacteriostatic capabilities. Further investigations unveil the antibacterial mechanisms of complex Cu-1, revealing its ability not only to suppress the activities of DNA gyrase and topoisomerases IV, but also to effectively inhibit biofilm formation and disrupt the integrity of cell membrane. This multi-targeting action contributes to mitigating the risk of bacterial resistance emergence. Additionally, synergy between Cu-1 and conventional antibiotics is confirmed through checkerboard assays, offering novel strategies for antibacterial therapy. In vivo experiments using a murine model of S.aureus infection demonstrate the significant antibacterial efficacy of Cu-1, providing robust support for its potential in treating S.aureus infections. This study demonstrates that the coordination complexes formed by copper, Gatifloxacin and suitable aromatic heterocyclic ligands exhibit multi-targeting characteristics against bacteria, offering a new direction for combating antibiotic resistance in antibacterial therapy.