Cobalt(II) and zinc(II) anthrahydrazone complexes: synthesis, crystal structure, divergent anticancer and antibacterial activities

Abstract

Two new metal complexes 9-AIH-Co and 9-AIH-Zn, were synthesized using (Z)-2-(2-(anthracen-9-ylmethylene)hydrazineyl)-4,5-dihydro-1H-imidazole (9-AIH) as the ligand and evaluated as anticancer agents. Their structures were determined by single-crystal X-ray diffraction, elemental analysis and mass spectroscopy. The 9-AIH ligand crystallized in acetate form within the orthorhombic crystal system with space group Pna2₁. The cobalt complex, 9-AIH-Co, is a mononuclear complex with chloride counterions, adopting a tetrahedral coordination geometry and crystallizing in the monoclinic system with space group P2₁/n. Similarly, the zinc complex, 9-AIH-Zn, with acetate counterions, also exhibits a tetrahedral configuration but crystallizes in the monoclinic system with space group C2/c. Anticancer activity assays revealed that 9-AIH-Co demonstrated significant inhibitory effects against three representative tumor cell lines, MGC-803 (gastric cancer), SK-OV-3 (ovarian cancer), and HepG-2 (liver cancer), which were selected for their clinical relevance as models for prevalent and challenging solid tumors. The IC₅₀ values were 6.45 ± 0.78, 8.28 ± 0.80 and 8.87 ± 2.26 µM, respectively, showing superior activity compared to both the free ligand 9-AIH and the 9-AIH-Zn. In vitro antibacterial tests indicated that 9-AIH-Co possessed antimicrobial properties similar to those of 9-AIH against four common pathogenic bacteria, including Bacillus subtilis, with MIC values ranging from 3.9 to 7.8 µg/mL. Conversely, 9-AIH-Zn showed markedly diminished antibacterial effects, with the MIC value of 125 µg/mL. These findings collectively suggest that metal ions play a pivotal role in modulating the comprehensive biological activities of metal complexes. The coordination of imidazole with Co(II) synergistically enhances both anticancer and antibacterial activities, whereas Zn(II) appears more appropriate for developing complexes with lower cytotoxicity. This research provides fundamental insights into the metal-ion-specific behavior of anthrahydrazone complexes, highlighting cobalt coordination as a promising strategy for developing dual-functional metallodrugs.