Novel benzyl-substituted molybdocene anticancer drugs

From the reaction of 6-(p-methoxyphenyl) fulvene (1a), 6-(3,4-dimethoxyphenyl) fulvene (1b) and 6-(3,4,5-trimethoxyphenyl) fulvene (1c) with LiBEt3H, lithiated cyclopentadienide intermediates (2a–c) were synthesised. These intermediates were then transmetallated to molybdocene using MoCl4 (synthesized in situ) to yield the benzyl-substituted molybdocenes bis-[(p-methoxybenzyl)cyclopentadienyl] molybdenum (IV) dichloride (3a), bis-[(3,4-dimethoxybenzyl)cyclopentadienyl] molybdenum (IV) dichloride (3b), and bis-[(3,4,5-trimethoxybenzyl)cyclopentadienyl] molybdenum (IV) dichloride (3c). The molybdocene 3a was characterised by single crystal X-ray diffraction. All three molybdocenes had their cytotoxicity investigated through MTT based preliminary in vitro testing on the human renal cell line Caki-1 in order to determine their IC50 values and compare them with the corresponding titanocene and vanadocene dichloride derivatives. Molybdocenes 3b–c were found to have the same IC50 values of 290 μM, while 3a yielded a value of 84 μM, respectively

Graphical abstractThree benzyl-substituted molybdocene dichloride complexes were synthesised through the hydridolithiation reaction of appropriately substituted fulvenes with LiBEt3H. Within, the synthesis of the three molybdocene derivatives are reported along with a structural discussion. Additionally, the compounds were tested for their anticancer activity.Figure optionsDownload full-size imageDownload as PowerPoint slide