Electrochemically driven supramolecular interaction of quinones and ferrocifens: an example of redox activation of bioactive compounds.

This review discusses the state of the art, challenges and perspectives in recent applications of electrochemistry in the life sciences. It deals mainly with the elucidation of molecular mechanisms of drug action, drug design and development, involving electron transfer, pharmaco-electrochemistry (the combination of electrochemical and pharmacological assays), and electrochemical studies of membrane models and drug delivery. It aims to shed light on the question: does electrochemistry really contribute to this area? It includes a general introduction for the use of electrochemistry in the life sciences, with a focus on how electrochemistry can uniquely provide both kinetic and thermodynamic information. A number of studies are reported in the literature and from the authors' laboratories, including the investigation of biooxidative/bioreductive activation of pro-drugs, DNA alkylation, electrochemically- based release of reactive oxygen and nitrogen species, with a particular emphasis on quinones, ferrocifens and compounds with mixed-functionality. Within the context of drug delivery and bioavailability, the electrochemical investigation of supramolecular interactions of the chosen classes of compounds with cyclodextrins and lipid bilayers, in relation to their solubilization and vectorization was also carried out. The updated examples herein illustrate how relevant and challenging the integration of electrochemistry, supramolecular and materials chemistry, biochemistry and medical knowledge for the design and development of redox-selective molecular approaches is. Many questions related to these fields are still unclear and the search for selectivity toward redox therapeutic agents remains of expanding interest. This review hopes to stimulate researchers to become more involved in this fruitful interface between electrochemistry and the life sciences.

Electrochemically Driven Supramolecular Interaction of Quinones and Ferrocifens: An Example of Redox Activation of Bioactive Compounds.

This review discusses the state of the art, challenges and perspectives in recent applications of electrochemistry in the life sciences. It deals mainly with the elucidation of molecular mechanisms of drug action, drug design and development, involving electron transfer, pharmaco-electrochemistry (the combination of electrochemical and pharmacological assays), and electrochemical studies of membrane models and drug delivery. It aims to shed light on the question: does electrochemistry really contribute to this area? It includes a general introduction for the use of electrochemistry in the life sciences, with a focus on how electrochemistry can uniquely provide both kinetic and thermodynamic information. A number of studies are reported in the literature and from the authors' laboratories, including the investigation of biooxidative/bioreductive activation of pro-drugs, DNA alkylation, electrochemically-based release of reactive oxygen and nitrogen species, with a particular emphasis on quinones, ferrocifens and compounds with mixed-functionality. Within the context of drug delivery and bioavailability, the electrochemical investigation of supramolecular interactions of the chosen classes of compounds with cyclodextrins and lipid bilayers, in relation to their solubilization and vectorization was also carried out. The updated examples herein illustrate how relevant and challenging the integration of electrochemistry, supramolecular and materials chemistry, biochemistry and medical knowledge for the design and development of redox-selective molecular approaches is. Many questions related to these fields are still unclear and the search for selectivity toward redox therapeutic agents remains of expanding interest. This review hopes to stimulate researchers to become more involved in this fruitful interface between electrochemistry and the life sciences.

Molecular mechanism of action of 2-ferrocenyl-1,1-diphenylbut-1-ene on HL-60 leukemia cells.

The aim of this work was to investigate the mechanism of action of 2-ferrocenyl-1,1-diphenylbut-1-ene (1) on HL-60 human leukemia cells. While inactive against noncancerous cells, 1 provoked a concentration-dependent decrease in viable tumor cells, primarily via apoptosis, as evidenced by analysis of cell morphology, activation of caspases 3 and 7, increased DNA fragmentation, and externalization of phosphatidylserine. Necrosis was observed only at the highest tested concentration (4 µM). Compound 1 interfered with the cell cycle, causing an accumulation of cells in the G1 /G0 phase. Interaction of 1 with dsDNA and ssDNA was observed by differential pulse voltammetry and confirmed by hyperchromicity in the UV/Vis spectra of dsDNA, with an interaction constant of 2×10(4) M(-1). Both the organic analogue 1,1,2-triphenylbut-1-ene (2) and ferrocene were inactive against cancer and noncancer cell lines and did not react with DNA. These results reinforce the idea that the hybrid strategy of conjugating ferrocene to the structure of tamoxifen derivatives is advantageous in finding new substances with antineoplastic activity.