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Synthesis and Cytotoxicity Studies of New (Dimethylamino)‐Functionalised and 7‐Azaindole‐Substituted ‘Titanocene’ Anticancer Agents (7‐Azaindole=1 H ‐Pyrrolo[2,3‐ b ]pyridine)
Author(s) -
Hogan Megan,
Cotter Juliet,
Claffey James,
Gleeson Brendan,
Wallis Denise,
O'Shea Donal,
Tacke Matthias
Publication year - 2008
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.200890191
Subject(s) - chemistry , fulvene , transmetalation , pyridine , stereochemistry , cytotoxicity , cytotoxic t cell , medicinal chemistry , lithium (medication) , organic chemistry , catalysis , biochemistry , medicine , in vitro , endocrinology
From the carbolithiation of 1‐(cyclopenta‐2,4‐dien‐1‐ylidene)‐ N , N ‐dimethylmethanamine (=6‐(dimethylamino)fulvene; 3 ) and different lithiated azaindoles 2 (1‐methyl‐7‐azaindol‐2‐yl, 1‐[(diethylamino)methyl]‐7‐azaindol‐2‐yl, and 1‐(methoxymethyl)‐7‐azaindol‐2‐yl), the corresponding lithium cyclopentadienide intermediates 4a – 4c were formed (7‐azaindole=1 H ‐pyrrolo[2,3‐ b ]pyridine). The latter underwent a transmetallation reaction with TiCl 4 resulting in the (dimethylamino)‐functionalised ‘titanocenes’ 5a – 5c . When the ‘titanocenes’ 5a – 5c were tested against LLC‐PK cells, the IC 50 values obtained were of 8.8, 12, and 87 μ M , respectively. The most cytotoxic ‘titanocene’, 5a , with an IC 50 value of 8.8 μ M is nearly as cytotoxic as cis ‐platin, which showed an IC 50 value of 3.3 μ M when tested on the epithelial pig kidney LLC‐PK cell line, and ca. 200 times better than ‘titanocene dichloride’ itself.