Dimethylamino-functionalised and N-heteroaryl-substituted titanocene anticancer drugs: synthesis and cytotoxicity studies

From the carbolithiation of 6-N,N-dimethylamino fulvene (3a) and different lithiated N-heterocyclic compounds (N,N-dimethylaminomethylpyrrole, 1-methylimidazole and 2,4-[bis(N',N'-dimethylaminomethyl)]-N-methyl pyrrole), the corresponding lithium cyclopentadienide intermediate (4a-c) was f...

Full description

Saved in:
Bibliographic Details
Published in:Investigational new drugs 2007-10, Vol.25 (5), p.425-433
Main Authors: Hickey, Thomas, Claffey, James, Fitzpatrick, Eoin, Hogan, Megan, Pampillón, Clara, Tacke, Matthias
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Apoptosis
Breast cancer
Cancer
Cell Survival - drug effects
Chemotherapy
Clinical trials
Cytotoxicity
Drugs
Kidney cancer
Lithium
LLC-PK1 Cells
Metastasis
Molecular Conformation
Molecular Structure
Organometallic Compounds - chemical synthesis
Organometallic Compounds - chemistry
Organometallic Compounds - pharmacology
Pharmacology
Prostate
Solvents
Swine
Titanium
Tumors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:From the carbolithiation of 6-N,N-dimethylamino fulvene (3a) and different lithiated N-heterocyclic compounds (N,N-dimethylaminomethylpyrrole, 1-methylimidazole and 2,4-[bis(N',N'-dimethylaminomethyl)]-N-methyl pyrrole), the corresponding lithium cyclopentadienide intermediate (4a-c) was formed. These three lithiated intermediates underwent a transmetallation reaction with TiCl4 resulting in dimethylamino-functionalised titanocenes 5a-c. When these titanocenes were tested against LLC-PK cells, the IC50 values obtained were of 13, and 63 microM for titanocenes 5b and 5c, respectively. The most cytotoxic titanocene in this paper (5a) with an IC50 value of 6.8 microM is found to be almost as cytotoxic as cis-platin, which showed an IC50 value of 3.3 microM, when tested on the epithelial pig kidney LLC-PK cell line, and titanocene 5c is approximately 400 times better than titanocene dichloride itself.
ISSN:0167-6997
1573-0646
DOI:10.1007/s10637-007-9061-8