Synthesis and Cytotoxicity Studies of Fluorinated Derivatives of Vanadocene Y

• Published in: European Journal of Inorganic Chemistry Vol. 2009; no. 19; pp. 2804 - 2810
• Main Authors: Gleeson, Brendan, Claffey, James, Deally, Anthony, Hogan, Megan, Méndez, Luis Miguel Menéndez, Müller-Bunz, Helge, Patil, Siddappa, Wallis, Denise, Tacke, Matthias
• Format: Book Review Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01.07.2009; WILEY‐VCH Verlag; Wiley
• Subjects: Antitumor agents; Cancer; Chemistry; Chemistry, Inorganic & Nuclear; Cytotox­icity; Drug design; Drug discovery; Fluorinated ligands; Hydridolithiation; Physical Sciences; Sandwich complexes; Science & Technology; Vanadium; Vanadocene; Fluorinated ligands; DICHLORIDE; APOPTOSIS; Vanadocene; BEHAVIOR; Vanadium; Hydridolithiation; Cytotoxicity; RENAL-CELL CARCINOMA; TRIAL; ACID COMPLEXES; Antitumor agents; Sandwich complexes; CISPLATIN; TITANOCENE ANTICANCER DRUGS; Drug design; Drug discovery; Cancer
• ISSN: 1434-1948; 1099-0682
• DOI: 10.1002/ejic.200900297

From the reaction of 6‐(2‐fluoro‐4‐methoxyphenyl)fulvene (1a), 6‐(3‐fluoro‐4‐methoxyphenyl)fulvene (1b) and 6‐[4‐(trifluoromethoxy)phenyl]fulvene (1c) with LiBEt3H, lithiated cyclopentadienide intermediates (2a–c) were synthesised. These intermediates were then transmetallated to vanadium with VCl4 to yield the benzyl‐substituted vanadocenes bis[(2‐fluoro‐4‐methoxybenzyl)cyclopentadienyl]vanadium(IV) dichloride (3a), bis[(3‐fluoro‐4‐methoxybenzyl)cyclopentadienyl]vanadium(IV) dichloride (3b), and bis[(4‐trifluoromethoxybenzyl)cyclopentadienyl]vanadium(IV) dichloride (3c). The three vanadocenes 3a–c were characterised by single‐crystal X‐ray diffraction. All three vanadocenes had their cytotoxicity investigated through MTT‐based preliminary in‐vitro testing on the LLC‐PK and Caki‐1 cell lines in order to determine their IC50 values. Vanadocenes 3a–c were found to have IC50 values of 6.0 (+/–4), 35 (+/–7) and 13 (+/–3) μM on the LLC‐PK cell line and IC50 values of 78 (+/–11), 18 (+/–16) and 2.2 (+/–0.5) μM on the Caki‐1 cell line respectively. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) Within, the syntheses of three fluorinated derivatives of the p‐methoxybenzyl‐substituted vanadocene dichloride, through the hydridolithiation reaction of appropriatelyfluoro‐substituted fulvenes with LiBEt3H, are reported along with structural discussion. Additionally, these compounds were tested for their anticancer activity.