Journal
CHEMMEDCHEM
Volume 16, Issue 11, Pages 1804-1812Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cmdc.202100060
Keywords
antitumor agents; cyclopentadienyl ligand; cytotoxicity; fulvene; MOLT-4
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Funding
- [Progres/UK Q40/01]
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Cytotoxic complexes containing molybdenum are studied as potential alternatives to commercial drugs, with different ligands having a significant impact on cytotoxicity. Functionalization of the Cp ring in Mo complexes can improve cytotoxicity against cancer cells, suggesting a potential strategy for designing highly efficient cytotoxic drugs in the future.
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 [(eta(5)-Cp ')Mo(CO)(2)(L-N,L-N)][BF4], where Cp is cyclopentadienyl and L-N,L-N is a bidentate ligand, are well known for their strong anticancer activity. It is a generally accepted paradigm that the nature of the coordinated L-N,L-N 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 pi-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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