Heteroaryl substituted titanocenes as potential anti-cancer drugs.
From the reaction of Super Hydride (LiBEt(3)H) with 6-(furyl)fulvene (1a), 6-(thiophenyl)fulvene (1b) or 6-(N-methyl-pyrrole)fulvene (1c) the corresponding lithium cyclopentadienide intermediates (2a-c) were obtained. These intermediates were reacted with titanium tetrachloride and bis-[(furyl-2-cyclopentadienylmethane)] titanium(IV) dichloride (3a) and bis-[(thiophenyl-2-cyclopentadienylmethane)] titanium(IV) dichloride (3b) and bis-[(N-methylpyrrole-2-cyclopentadienylmethane)] titanium(IV) dichloride (3c) were obtained and subsequently characterised by X-ray crystallography. When titanocenes 3a-c were tested against pig kidney (LLC-PK) cells inhibitory concentrations (IC(50)) of 1.6x10(-4)M, 1.5x10(-4)M and 9.1x10(-4)M, respectively, were observed. These values represent improved cytotoxicity against LLC-PK, when compared to their corresponding ansa substituted analogues and also in comparison to unsubstituted titanocene dichloride.
Sweeney
Nigel
N
Conway Institute of Biomolecular and Biomedical Research, The UCD School of Chemistry and Chemical Biology, Centre for Synthesis and Chemical Biology (CSCB), Belfield, Dublin 4, Ireland.
Gallagher
William M
WM
Müller-Bunz
Helge
H
Pampillón
Clara
C
Strohfeldt
Katja
K
Tacke
Matthias
M
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D002470:Cell Survival; D004353:Drug Evaluation, Preclinical; D008968:Molecular Conformation; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry*; D013552:Swine
D000970:Antineoplastic Agents; D009942:Organometallic Compounds; C406884:titanocene