ABSTRACT
In this work the synthesis and characterization of new gold(III) complexes with quinoline ligands are described. These complexes contain different steric and electronic properties of the donor atom at 8-position of the quinoline in order to modulate their stability and their biological activity. Their redox potential, stability in organic and aqueous solvents, and their biological activity in a panel of six different human tumor cell lines are also presented. In addition, interaction studies of the complexes with model biological molecules (pBR322 and L-acetyl-N-cysteine) were carried out, suggesting that their main target are proteins. From these studies, we have found that the gold(III) complex with an N-tosyl-8-aminoquinoline ligand is the most active complex in all the tumor cell lines, including the cisplatin resistant T-47D and WiDr cell lines. Moreover, this complex showed to be the most stable compound in DMSO and saline solution, even after several hours.
Subject(s)
Antineoplastic Agents , Cell Proliferation/drug effects , Neoplasms/drug therapy , Organogold Compounds , Quinolines , A549 Cells , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Electrochemical Techniques , HeLa Cells , Humans , Neoplasms/metabolism , Neoplasms/pathology , Organogold Compounds/chemical synthesis , Organogold Compounds/chemistry , Organogold Compounds/pharmacology , Quinolines/chemical synthesis , Quinolines/chemistry , Quinolines/pharmacologyABSTRACT
In this article, we report on the synthesis and the chemical and biological characterization of novel gold(III) complexes based on hydroxyl- or amino-quinoline ligands that are evaluated as prospective anticancer agents. To gain further insight into their reactivity and possible mode of action, their interactions with model proteins and standard nucleic acid molecules were investigated.
Subject(s)
Antineoplastic Agents/chemical synthesis , DNA/chemistry , Electron Transport Complex IV/chemistry , Organogold Compounds/chemical synthesis , Quinolines/chemistry , Amino Acid Sequence , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Cell Survival/drug effects , Electron Transport Complex IV/metabolism , Humans , Ligands , Molecular Sequence Data , Organogold Compounds/chemistry , Organogold Compounds/pharmacology , Organogold Compounds/toxicity , Protein BindingABSTRACT
The asymmetric synthesis of tricyclic compounds by the desymmetrization of cyclohexadienones is presented. The reaction tolerated a large variety of substituents at different positions of the cyclohexadienone, and heterocyclic rings of different sizes were accessible. Density functional theory calculations showed that the reaction proceeds through an asynchronous [4+2] cycloaddition.
Subject(s)
Cyclohexenes/chemistry , Crystallography, X-Ray , StereoisomerismABSTRACT
In this communication, we present the synthesis of new platinum complexes based on hydroxyquinoline ligands. We demonstrate the importance and the role of the halogen substitution as well as the chelation, which are essential structural characteristics for finding good cytotoxicities.
Subject(s)
Antineoplastic Agents/pharmacology , Clioquinol/chemistry , Halogens/chemistry , Hydroxyquinolines/chemistry , Organoplatinum Compounds/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Crystallography, X-Ray , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , HeLa Cells , Humans , Ligands , Models, Molecular , Molecular Structure , Organoplatinum Compounds/chemical synthesis , Organoplatinum Compounds/chemistry , Structure-Activity RelationshipABSTRACT
The use of a catalytic amount of platinum complexes (1 mol %) was found to be compatible with different organocatalysts (DABCO or the Jørgensen-Hayashi catalyst) that were used in the functionalization of various activated methylenes. By this method, a series of lactones with C-3 quaternary centers and substitution at C-5 were prepared.
