Morpholino-Functionalized and Heteroaryl-Substituted Titanocene Anti-Cancer Drugs: Synthesis and Cytotoxicity Studies

From the carbolithiation of 6‐morpholino fulvene (3a) and different ortho‐lithiated heterocycles (furan, thiophene and N‐methylpyrrole), the corresponding lithium cyclopentadienide intermediate (4a–c) was formed. These three lithiated intermediates underwent a transmetallation reaction with TiCl4 re...

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Bibliographic Details
Published in:Zeitschrift für anorganische und allgemeine Chemie (1950) 2007-08, Vol.633 (10), p.1695-1700
Main Authors: Pampillón, Clara, Claffey, James, Hogan, Megan, Tacke, Matthias
Format: Article
Language:English
Subjects:
Anti-cancer drugs
cis-Platin
Fulvene
Heteroaryl-substituted metallocene
Morpholino-functionalized metallocene
Titanocene
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Summary:From the carbolithiation of 6‐morpholino fulvene (3a) and different ortho‐lithiated heterocycles (furan, thiophene and N‐methylpyrrole), the corresponding lithium cyclopentadienide intermediate (4a–c) was formed. These three lithiated intermediates underwent a transmetallation reaction with TiCl4 resulting in morpholino‐functionalised titanocenes 5a–c. When these titanocenes were tested against LLC‐PK cells, the IC50 values obtained were of 58, 63 and 115 μM for titanocenes 5a–c respectively. The most cytotoxic titanocene 5a with an IC50 value of 58 μM is found to be approximately 20 times less cytotoxic than cis‐platin, which showed an IC50 value of 3.3 μM, when tested on the LLC‐PK cell line, and 10 times less cytotoxic than its dimethylamino‐functionalised analogue (Titanocene C, IC50 = 5.5 μM).
ISSN:0044-2313
1521-3749
DOI:10.1002/zaac.200700212