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Anticancer diaminotris(phenolato) vanadium(V) complexes: Ligand-metal interplay

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Vanadium complexes are attractive candidates for anticancer chemotherapy, although often suffering from rich aqueous chemistry and hydrolytic instability. We have introduced an LVO family of vanadium oxo complexes, L being a diaminotris(phenolato) chlelating ligand, demonstrating high hydrolytic stability in water along with promising in vitro and in vivo efficacy. Herein we analyzed mechanistic aspects of the reactivity of such complexes in cellular environment. A representative complex exhibited high activity toward all lines in the NIH NCI-60 panel, with an average GI50 value of 0.7 ± 0.5 μM, and with a unique reactivity pattern implying a distinct mechanism. Free ligands demonstrated cytotoxicity similar to that of their vanadium complexes, were identified in cells treated with the complex, and induced apoptosis as did the parent complex, all implying their participation as active species. Cell cycle studies pointed to possible arrest mostly at the S phase, with some variations for the complex and ligand on the two lines analyzed. Nevertheless, the vanadium ion apparently accelerated cellular entry, as the activity was evident following markedly shorter periods of incubation with the extracellular complex when compared with the free ligand. The results displayed herein overall highlight the role of the vanadium complex as a pro-drug.
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Keywords: Vanadium(V); anticancer; cisplatin; cytotoxicity; in vitro; metallodrugs

Document Type: Research Article

Affiliations: 1: Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem, Israel 2: Department of Cell and Development Biology Alexander, Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel

Publication date: July 3, 2018

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