Department of General and Inorganic Chemistry, Faculty of Chemical Technology, University of Pardubice, Studentská 573, 532 10, Pardubice, Czech Republic.
Department of Analytical Chemistry, Faculty of Chemical Technology, University of Pardubice, Studentská 573, 53210, Pardubice, Czech Republic.
ChemMedChem. 2021 Jun 7;16(11):1804-1812. doi: 10.1002/cmdc.202100060. Epub 2021 Mar 24.
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 [(η -Cp')Mo(CO) ( L)][BF ], where Cp is cyclopentadienyl and 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 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 IC 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.
含钼的细胞毒性配合物被广泛研究作为商业使用的药物的潜在替代品，这些药物往往具有明显的副作用和细胞耐药性。[(η-Cp')Mo(CO)(L)][BF] 型化合物，其中 Cp 是环戊二烯基，L 是双齿配体，因其具有很强的抗癌活性而广为人知。人们普遍认为，配位 L 配体的性质对细胞毒性有重大影响。在这项研究中，一系列新型功能化的钼 Cp 配合物是由衍生的富烯作为 π-配体前体制备的。事实上，通过各种 N，N-螯合配体对配位球的调制提供了对白血病细胞系 MOLT-4 具有活性的物种，IC 值取决于所用的 N，N-螯合剂的性质。然而，后续研究清楚地表明，Cp 环用胺基部分进行功能化可大大提高细胞毒性。这些结果对未来设计高效抗癌药物至关重要，因为人们认为环戊二烯基的修饰对生物活性的影响较小。
