Synthesis and Cytotoxicity Studies of New (Dimethylamino)‐Functionalised and 7‐Azaindole‐Substituted ‘Titanocene’ Anticancer Agents (7‐Azaindole=1H‐Pyrrolo[2,3‐b]pyridine) |
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Authors: | Megan Hogan Juliet Cotter James Claffey Brendan Gleeson Denise Wallis Donal O'Shea Matthias Tacke |
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Affiliation: | UCD School of Chemistry and Chemical Biology, Conway Institute of Biomolecular and Biomedical Research, Centre for Synthesis and Chemical Biology (CSCB), University College Dublin, Belfield, Dublin 4, Ireland |
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Abstract: | 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=1H‐pyrrolo[2,3‐b]pyridine). The latter underwent a transmetallation reaction with TiCl4 resulting in the (dimethylamino)‐functionalised ‘titanocenes’ 5a – 5c . When the ‘titanocenes’ 5a – 5c were tested against LLC‐PK cells, the IC50 values obtained were of 8.8, 12, and 87 μM , respectively. The most cytotoxic ‘titanocene’, 5a , with an IC50 value of 8.8 μM is nearly as cytotoxic as cis‐platin, which showed an IC50 value of 3.3 μM when tested on the epithelial pig kidney LLC‐PK cell line, and ca. 200 times better than ‘titanocene dichloride’ itself. |
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Keywords: | Anticancer activity cis‐Platin ‘ Titanocene’ Fulvene (Dimethylamino)‐functionalized metallocenes Metallocenes 7‐Azaindoles Azaindolyl‐substituted metallocenes 1H‐Pyrrolo[2,3‐b]pyridines |
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