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Ruthenium(II)/diphosphine/naphthoquinone complexes: synthesis; characterization; anticancer activity and molecular docking studies
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DOI：10.1039/D6DT00204H.png)
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Abstract
En 中文
Breast cancer (BC) is one of the most challenging types of cancer in women. Triple-negative breast cancer (TNBC) is an aggressive and rapidly progressive subtype that lacks targeted therapies; relying primarily on chemotherapy. Given the limited treatment options for TNBC; novel therapeutic strategies are needed to address this disease. In this context; here we report the synthesis and characterization of four ruthenium(II) complexes containing naphthoquinone derivatives as ligands: [Ru(NQ1)(bipy)(dppen)]PF6 (Ru1); [Ru(NQ2)(bipy)(dppen)]PF6 (Ru2); [Ru(NQ1)(bipy)(DPEphos)]PF6 (Ru3); and [Ru(NQ2)(bipy)(DPEphos)]PF6 (Ru4); where bipy = 2; 2′-bipyridine; dppen = 1; 2-bis(diphenylphosphino)ethylene; DPEphos = bis[(2-diphenylphosphino)phenyl]ether; and NQ1 and NQ2 = deprotonated lawsone and lapachol; respectively. Mass spectrometry and elemental analyses were used to confirm the purity of the complexes. In vitro assays showed that Ru1–Ru4 were cytotoxic against MDA-MB-231 and MCF-7 (breast cancer cell lines) and A549 (lung cell line). The compounds exhibited lower IC50 values than cisplatin; used as a control. Ru4 was the most promising compound; with the highest selectivity index for the triple-negative breast cancer cell line (SI = 25.5). Furthermore; this complex inhibited colony formation; induced apoptosis; and affected the cell cycle in these cancer cells. Western blot analysis showed increased cleaved caspase-3 expression; corroborating the apoptotic mechanism observed by flow cytometry. Furthermore; cell uptake studies showed that ruthenium was found at the intracellular level after treatment with the MDA-MB-231 cell line. DNA-binding studies revealed an interaction between Ru1–Ru4 and Ct-DNA via the minor groove pocket; as confirmed by molecular docking. Overall; our results suggest [Ru(NQ2)(bipy)(DPEphos)]PF6 (Ru4) to be a promising cytotoxic agent against breast cancer.
Keywords:
ruthenium complexes
naphthoquinone derivatives
triple-negative breast cancer
anticancer activity
molecular docking
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