Anticancer activity of Nickel(II) tetraazamacrocyclic monochloro complex against MCF-7 and Ehrlich ascites carcinoma models

Cancer, a major global health concern, driving the need to develop new treatments modalities that are more effective and safer. To find out effective and safe chemo-agent, a new nickel(II) tetraazamacrocyclic monochloro complex, [(Ni- Me 8 [14]diene)(Cl)](Cl), was synthesized and tested on anticancer activity using in vitro and in vivo models in this study. Initial cytotoxicity was determined through the brine shrimp lethality assay with an LC 50 of 15.57 µg/mL. The compound reduced the growth of MCF-7 human breast cancer cells in a dose-dependent manner, with an IC₅₀ value of 55.57 µg/mL. Morphological examination showed that there was condensation, fragmentation, and formation of apoptotic bodies in the nuclei, indicating the induction of apoptosis. RT-PCR results indicated increased expression of pro-apoptotic genes ( p53 , BAX , PARP1 , CASP3 , CASP8 , and CASP9 ) along with reduced expression of the anti-apoptotic gene BCL2 . In vivo testing with the Ehrlich ascites carcinoma (EAC) model demonstrated significant tumor growth inhibition, 82.12 and 87.82% at doses of 100 and 200 µg/kg/day, respectively ( p < 0.01). Mice that were treated gained less tumor associated weight by 32.61% and 41.30% ( p < 0.01) and extended the mean survival time by 43.59% and 53.85% at 100 and 200 µg/kg/day, respectively ( p < 0.05). The hematological parameters partially returned to normal in EAC-bearing animals receiving the treatment. Biochemical analysis and the histopathology of the main organs showed minimal or no toxicity of the compound. Also, DFT calculations such as geometry optimization, MEP mapping, HOMO-LUMO analysis, quantum reactivity descriptors, and DOS spectra, provided insights into the compound’s reactivity, stability, electron-transfer properties, and electronic characteristics. These results indicate the fact that [(Ni- Me 8 [14]diene)(Cl)](Cl) can suppress tumor growth, potentially through apoptosis-related mechanisms, and showed preliminary short-term tolerability. The findings indicate that it has the potential to be a good candidate in further preclinical studies, including comprehensive safety and selectivity assessment, towards its development as an anticancer therapeutic agent.