Cyclopentadienyl-Based Anticancer Drugs: Improvement of Cytotoxic Activity through Functionalisation of the π Ligand
Language English Country Germany Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
Grant support
Q40/01
Charles University, Czech Republic
- Keywords
- MOLT-4, antitumor agents, cyclopentadienyl ligand, cytotoxicity, fulvene,
- MeSH
- Cell Line MeSH
- Cyclopentanes chemistry pharmacology MeSH
- Coordination Complexes chemical synthesis chemistry pharmacology MeSH
- Humans MeSH
- Ligands MeSH
- Molecular Structure MeSH
- Molybdenum chemistry pharmacology MeSH
- Cell Proliferation drug effects MeSH
- Antineoplastic Agents chemical synthesis chemistry pharmacology MeSH
- Drug Screening Assays, Antitumor MeSH
- Dose-Response Relationship, Drug MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Cyclopentanes MeSH
- Coordination Complexes MeSH
- Ligands MeSH
- Molybdenum MeSH
- Antineoplastic Agents MeSH
Cytotoxic complexes containing molybdenum are widely studied as a potential substitution for commercially used drugs that often suffer from pronounced side effects and cellular resistance. Compounds of the type [(η5 -Cp')Mo(CO)2 (N,N L)][BF4 ], where Cp is cyclopentadienyl and N,N L is a bidentate ligand, are well known for their strong anticancer activity. It is a generally accepted paradigm that the nature of the coordinated N,N L ligand has a major impact on the cytotoxicity. In this study, a series of new functionalised Cp complexes of molybdenum was synthesised from derivatised fulvenes as π-ligand precursors. Indeed, the coordination sphere's modulation by various N,N-chelating ligands afforded species active toward leukemic cell line MOLT-4 with IC50 values depending on the character of the N,N-chelator used. However, following study clearly showed that functionalisation of the Cp ring with an amine moiety considerably improved cytotoxicity. These results are of crucial importance for the future design of highly active cytotoxic drugs, as modification of cyclopentadienyl is believed to have a minor effect on biological activity.
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