Can Substitution of Chlorides Enhance the Cytotoxicity of Vanadocene Dichloride?

Abstract

A series of vanadocene complexes [Cp′2V(L)][OTf]2 (Cp′ = η5‐C5H5, η5‐C5H4Me; L = phen, 5‐NO2‐phen, 5‐NH2‐phen, 4,7‐Ph2‐phen) was prepared and characterized by mass spectrometry and EPR spectroscopy. Structures of two complexes that contain an N,N′‐chelating ligand, [(η5‐C5H4Me)2V(phen)][OTf]2·0.5Me2CO and [(η5‐C5H5)2V(5‐NH2‐phen)][OTf]2, and the triflate intermediate [(η5‐C5H5)2V(OTf)2] were further confirmed by X‐ray diffraction analysis. The cytotoxicity study has shown that complexes that contain phenanthroline ligands have considerably higher in vitro activity toward human leukemia cells MOLT‐4 and HL‐60 than their parent dichlorides ([Cp′2VCl2]). The high activity of these complexes coheres with their higher stability in various aqueous media. This study has further shown that substitution of chloride ligands in the vanadocene dichloride has a considerably higher effect on cytotoxicity than expected on the basis of established mechanistic rules.

Synthesis, characterization and cytotoxic activity of vanadocene dithiocarbamate complexes

“…The promising activity was observed for derivatives of cyclic dithiocarmatates. Their IC50 values are comparable with derivatives bearing modified 1,10-phenantholine ligands [23] and about one order of magnitude lower than reported for cisplatin [44].…”

“…Another approach for the design of highly active vanadocene species involves exchange of chloride ligands. Indeed, various metallocene species bearing N,N-chelating ligands exhibit increased in vitro cytotoxicity toward various leukemia cell lines [23][24][25].…”

Ring‐functionalized niobocene complexes

“…The highest cytotoxic effect was detected at the derivative bearing 2,4‐dimethoxybenzyl groups ( 17 ). The IC 50 value of this compound was found to be about three times lower than observed for unsubstituted niobocene dichloride and comparable with cisplatin (15.8 ± 1.9 μ m ) …”

“…One of few examples, where this approach leads to highly cytotoxic compounds, was published recently. Vanadocene complex bearing 5‐amino‐1,10‐phenanthroline [Cp 2 V(5‐NH 2 ‐phen)][OTf] 2 is about 20 times more active toward leukemia cells (MOLT‐4) than the parent dichloride species (Cp 2 VCl 2 ) as a result of the higher stability in aqueous media . Another promising approach for design of the highly active metallocene species involves modification of the [Cp 2 M] 2+ moiety through substitution in the cyclopentadienyl rings.…”

Highly Water‐Soluble Cyclopentadienyl and Indenyl Molybdenum(II) Complexes – Second Generation of Molybdenum‐Based Cytotoxic Agents

“…[19] All the compounds under the study (15)(16)(17)(18)(19)(20)(21)(22)(23) are highly active against both cell lines. Their IC50 values are much lower than reported for DDP, see Table 3.…”