Cyclopentadienyl‐Based Anticancer Drugs: Improvement of Cytotoxic Activity through Functionalisation of the π Ligand

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,NL)][BF4], where Cp is cyclopentadienyl and N,NL is a bidentate ligand...

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Bibliographic Details
Published in:ChemMedChem 2021-06, Vol.16 (11), p.1804-1812
Main Authors: Absolonová, Monika, Melounková, Lucie, Vinklárek, Jaromír, Honzíček, Jan, Dostál, Libor, Mrózek, Ondřej
Format: Article
Language:English
Subjects:
Anticancer properties
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Antineoplastic drugs
Antitumor activity
Antitumor agents
Biological activity
Biological effects
Cancer
Cell Line
Cell Proliferation - drug effects
Chelation
Coordination Complexes - chemical synthesis
Coordination Complexes - chemistry
Coordination Complexes - pharmacology
Coordination compounds
cyclopentadienyl ligand
Cyclopentanes - chemistry
Cyclopentanes - pharmacology
Cytotoxicity
Design modifications
Dose-Response Relationship, Drug
Drug development
Drug Screening Assays, Antitumor
Drugs
fulvene
Humans
Leukemia
Ligands
Molecular Structure
MOLT-4
Molting
Molybdenum
Molybdenum - chemistry
Molybdenum - pharmacology
Side effects
Toxicity
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Summary: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,NL)][BF4], where Cp is cyclopentadienyl and N,NL 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,NL 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. Cytotoxicity improvement: Series of Mo‐based cytotoxic compounds bearing both an N,N‐chelating ligand and cyclopentadienyl (Cp) substituted by amine group were prepared. Although the derivatisation of Cp has a minor impact on IC50 values, the introduction of amine increased the cytotoxic effect considerably.
ISSN:1860-7179
1860-7187
DOI:10.1002/cmdc.202100060