Synthesis and preliminary cytotoxicity studies of achiral pyrrolyl-substituted titanocenes

摘要

From the reaction of various 6-pyrrolylfulvenes (3a-3d) with Super Hydride (LiBEt_3H), lithiated cyclopentadienide intermediates (4a-4d) were synthesised. These intermediates were then transmetallated with titanium tetrachloride TiCl_4 to yield the pyrrolyl-substituted titanocenes bis-[((1-(4-methoxybenzyl)-pyrrole)2-)cyclopentadienyl]titanium(IV) dichloride (5a), bis-[((1-(4-methoxyphenyl)-pyrrole)2-)cyclopentadienyl]titanium(IV) dichloride (5b), bis-[((2,4-bis(4-methoxyphenyl)-1-methyl-pyrrole)2-) cyclopentadienyl]titanium(IV) dichloride (5c), bis-[((2-(4-methoxyphenyl)-1- methyl-pyrrole)2-)cyclopentadienyl]titanium(IV) dichloride (5d). Titanocene 5b crystallised and was characterised by X-ray crystallography. The four titanocenes 5a-5d were tested for their cytotoxicity through MTT-based in vitro tests on CAKI-1 cell lines in order to determine their IC_(50) values. Titanocenes 5a-5d were found to have IC_(50) values of 440 (±35), 68 (±14), 105 (±30), and 36 (±7) μM.