Abstract
Six new titanocene compounds have been isolated and characterised. These compounds were synthesised from their fulvene precursors using Super Hydride (LiBEt3H) followed by transmetallation with titanium tetrachloride to yield the corresponding titanocene dichloride derivatives. These complexes are bis-[((1-methyl-3-diethylaminomethyl)indol-2-yl)methylcyclopentadienyl] titanium (IV) dichloride (5a), bis-[((5-methoxy-1-methyl,3-diethylaminomethyl)indol-2-yl)methylcyclopentadienyl] titanium (IV) dichloride (5b), bis-[((1-methyl,3-diethylaminomethyl)indol-4-yl)methylcyclopentadienyl] titanium (IV) dichloride (5c), bis-[((5-bromo-1-methyl)indol-3-yl)methylcyclopentadienyl] titanium (IV) dichloride (5d), bis-[((5-chloro-1-methyl)indol-3-yl)methylcyclopentadienyl] titanium (IV) dichloride (5e), and bis-[((5-fluoro-1-methyl)indol-3-yl)methylcyclopentadienyl] titanium (IV) dichloride (5f). All six titanocenes 5a–5f were tested for their cytotoxicity through MTT-based in vitro tests on CAKI-1 cell lines using DMSO and Soluphor P as solubilising agents in order to determine their IC50 values. Titanocenes 5a–5f were found to have IC50 values of 10 (±2), 21 (±3), 29 (±4), 140 (±6), and 450 (±10) μM when tested using DMSO.
Highlights
Titanium-based reagents have been investigated for their use as anticancer agents for more than a decade and have been shown to have significant potential against solid tumours
The compound looked very promising during its preclinical evaluation; studies showed that an Ehrlich ascites cure of 100% and Colon 38 adenocarcinoma inhibition was better than that of cisplatin [3]
One of the main downfalls of titanocene dichloride being used in the clinic was the uncertainty regarding the composition of the biologically active titanium species responsible for the antitumor activity
Summary
Titanium-based reagents have been investigated for their use as anticancer agents for more than a decade and have been shown to have significant potential against solid tumours. Allen et al overcame the solubility issues of titanocene dichloride by incorporation of alkyl ammonium salts to the Cp ring to produce water soluble derivatives of titanocene dichloride [11] These compounds were shown to have significantly better activity and stability than their nonfunctionalized counterpart titanocene dichloride and gave a potent cytotoxic effect on cisplatin-resistant ovarian A2780 tumor cell lines. Substitution of the indole with a dimethylamino methyl arm and subsequent protonation of the amine with HCl gave the hydrochloride salt bis[(1methyl-3-dimethylaminomethyl)indol-2-yl)methylcyclopentadienyl] titanium (IV) dichloride 1b This compound was tested on the renal cell carcinoma cell line CAKI-1 to give an IC50 value of 13 μM when tested without any solubilising agent, and 0.71 μM when tested with the solubilising agent soluphor P [15]. We report the synthesis and cytotoxicity of novel achiral indole-substituted titanocene dichloride derivatives, which explore subtle structural changes to 1b
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
