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J Med Chem ; 57(14): 6252-8, 2014 Jul 24.
Article in English | MEDLINE | ID: mdl-24950478

ABSTRACT

We have synthesized and characterized a panel of new binuclear mixed valence Cu(I,II) complexes containing substituted 2-alkylthio-5-arylmethylene-4H-imidazolin-4-ones with unusual structure. These complexes are shown to be cytotoxic for various cell lines. We have found that these compounds did not intercalate DNA, inhibited number of polymerases (telomerase predominantly), accumulated in the cell nucleus, and caused DNA degradation. Preliminary studies revealed that lead compound inhibited human breast adenocarcinoma growth in mice model.


Subject(s)
Antineoplastic Agents/pharmacology , Copper/chemistry , Neoplasms, Experimental/drug therapy , Organometallic Compounds/pharmacology , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Crystallography, X-Ray , DNA Damage , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , HEK293 Cells , Hep G2 Cells , Humans , MCF-7 Cells , Mice , Mice, Inbred C57BL , Models, Molecular , Molecular Structure , Neoplasms, Experimental/pathology , Organometallic Compounds/chemical synthesis , Organometallic Compounds/chemistry , Structure-Activity Relationship
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