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Please use this identifier to cite or link to this item: http://hdl.handle.net/1974/1208

Title: A novel series of titanocene dichloride derivatives: synthesis, characterization and assessment of their cytotoxic properties
Authors: Potter, Gregory David

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Keywords: Organometallic
Anticancer
Titanocene dichloride
Issue Date: 2008
Series/Report no.: Canadian theses
Abstract: Although cis-PtCl2(NH3)2 (cisplatin) has been widely used as a chemotherapeutic agent, its use can be accompanied by toxic side effects and the development of drug resistance. Consequently, much research has been focused on the discovery of novel transition metal compounds which elicit elevated cytotoxicities coupled with reduced toxic side effects and non-cross resistance. Recently, research in this lab has focused on preparing derivatives of titanocene dichloride (TDC), a highly active chemotherapeutic agent, with pendant alkylammonium groups on one or both rings. Earlier results have demonstrated that derivatives containing either cyclic or chiral alkylammonium groups had increased cytotoxic activities. This research therefore investigated a new series of TDC complexes focusing specifically on derivatives bearing cyclic and chiral alkylammonium groups. A library of ten cyclic derivatives and six chiral derivatives were synthesized and fully characterized. These derivatives have undergone in vitro testing as anti-tumour agents using human lung, ovarian, and cervical carcinoma cell lines (A549, H209, H69, H69/CP, A2780, A2780/CP and HeLa). These standard cell lines represent solid tumour types for which new drugs are urgently needed. The potencies of all of the Ti (IV) derivatives varied greatly (range from 10.8 μM - >1000 μM), although some trends were observed. In general, the dicationic analogues exhibited greater potency than the corresponding monocationic derivatives. Additionally, the cyclic analogues bearing 1,3- and 1,4-substituted pyridines displayed potent cytotoxic activities (IC50> 20 μM). It was also found at concentrations of ~30 μM that the derivatives bearing an ephedrine derived substituent were cytotoxic. Conversely, analogues substituted with piperidinyl, morpholinyl or primary alkylammonium groups were inactive (>200 μM) against the cancer cell lines assayed.
Description: Thesis (Ph.D, Chemistry) -- Queen's University, 2008-05-14 13:18:28.141
URI: http://hdl.handle.net/1974/1208
Appears in Collections:Queen's Theses & Dissertations
Chemistry Graduate Theses

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