Browsing by Author "almalki, abrar"

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is there evidence in the literature supporting the use of structure-activity(SAR) relationships in cobalt complexes for the treatment of breast cancer, using MCF-7 as a cellular model?
(Saudi Digital Library, 2025) almalki, abrar; canelon, isolda
Breast cancer remains a major global health burden, with limitations in current therapies driving the search for novel agents. Transition-metal complexes, particularly cobalt-based compounds, have attracted attention due to their redox-based mechanism of action in hypoxic tumours. This systematic review critically evaluated whether evidence in the literature supports the use of structure-activity relationships (SAR) in cobalt complexes for the treatment of breast cancer, with a specific focus on the MCF-7 cell line as a representative in vitro model. A comprehensive search of Scopus (2015–2025) identified 29 eligible studies, yielding 61 distinct cobalt complexes tested in MCF-7 cells. Data were systematically extracted using a PICO framework and normalised by the cisplatin factor to enhance comparability. Findings revealed that several cobalt complexes demonstrated cytotoxic potency comparable to or exceeding cisplatin. However, no consistent direct structure–activity relationship (SAR) was observed for oxidation state, aromaticity, or halogenation. Instead, these factors appear to influence activity indirectly. The analysis showed no consistent direct relationship between oxidation state, aromaticity, or halogenation and cytotoxicity in MCF-7 cells. Evidence indicates that these features contribute indirectly: Co(III) complexes may act as prodrugs activated in hypoxic conditions, while Co(II) species are more reactive but less stable. Aromatic rings and halogens can also enhance lipophilicity, DNA stacking, and membrane permeability. Cobalt SAR is influenced by multiple factors, and context-dependent rather than linear. Progressive filtering reduced the dataset to 29 studies (61 complexes), excluding non- numerical results and inconsistent reporting. Normalisation using the cisplatin factor allowed cross-study comparisons despite differences in assays and exposure times. Although this reduced statistical power, it improved reproducibility and highlighted methodological weaknesses such as poor reporting of controls and recovery times. The refined dataset provides a reliable but selective foundation for future SAR studies. Cobalt complexes exhibit significant potential as anticancer agents in breast cancer models, but it requires expanded datasets, mechanistic assays, and in vivo validation. Future studies must prioritise standardisation, broader cell models, and exploration of combination therapies to fully establish cobalt’s role in oncology.
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