The interaction with DNA and with non-ionic micelles of new methyl-pyridinium and methyl-quinolinium derivatives, which showed good cytotoxicity in some cell lines, was investigated by UV-VIS spectroscopy and stationary fluorimetry. Also transient absorption spectroscopy with ns resolution, for detecting triplet and radicals formation, and with fs resolution, for ultrafast dynamics of singlet excited states, was performed. Spectrophotometric and fluorimetric titrations by adding salmon testes DNA provided evidence of a strong interaction between the quaternized azinium salts investigated and the polynucleotide, with binding constants of about 105÷106 M-1. Fluorimetric titrations showed a considerable enhancement of emission quantum yield, in agreement with a more rigid structure of the compounds involved in the binding with DNA. The predominant interaction mode, intercalation or groove binding, has been also investigated. Preliminary measurements by confocal fluorescence microscopy on cell lines in presence of the studied azinium salts will be performed with the aim to localize the compounds into cellular districts. Interaction between the azinium salts and some non-ionic surfactants was studied in order to find agents for drug solubilization and drug delivery. To check the ability of the micelles to encapsulate the studied salts into their hydrophobic core and to release them in presence of DNA, spectrophotometric and fluorimetric titrations were performed. Another proof of compounds encapsulation in micellar aggregates was obtained by ultrafast absorption spectroscopy, which demonstrated a slowdown of excited states dynamics in presence of surfactants, with respect to that of free compounds in aqueous medium. The obtained results suggested that the studied polar non-ionic micelles can act as promising drug delivery agents in order to minimize drug loss and degradation (preventing harmful side effects), to increase drug bioavailability and to release drugs into the cellular nuclei allowing their interaction with DNA.
Spectroscopic Investigation of the Molecular Interaction of New Potential Anticancer Drugs with DNA and Non-Ionic Micelles
MIOLO, GIORGIA;
2014
Abstract
The interaction with DNA and with non-ionic micelles of new methyl-pyridinium and methyl-quinolinium derivatives, which showed good cytotoxicity in some cell lines, was investigated by UV-VIS spectroscopy and stationary fluorimetry. Also transient absorption spectroscopy with ns resolution, for detecting triplet and radicals formation, and with fs resolution, for ultrafast dynamics of singlet excited states, was performed. Spectrophotometric and fluorimetric titrations by adding salmon testes DNA provided evidence of a strong interaction between the quaternized azinium salts investigated and the polynucleotide, with binding constants of about 105÷106 M-1. Fluorimetric titrations showed a considerable enhancement of emission quantum yield, in agreement with a more rigid structure of the compounds involved in the binding with DNA. The predominant interaction mode, intercalation or groove binding, has been also investigated. Preliminary measurements by confocal fluorescence microscopy on cell lines in presence of the studied azinium salts will be performed with the aim to localize the compounds into cellular districts. Interaction between the azinium salts and some non-ionic surfactants was studied in order to find agents for drug solubilization and drug delivery. To check the ability of the micelles to encapsulate the studied salts into their hydrophobic core and to release them in presence of DNA, spectrophotometric and fluorimetric titrations were performed. Another proof of compounds encapsulation in micellar aggregates was obtained by ultrafast absorption spectroscopy, which demonstrated a slowdown of excited states dynamics in presence of surfactants, with respect to that of free compounds in aqueous medium. The obtained results suggested that the studied polar non-ionic micelles can act as promising drug delivery agents in order to minimize drug loss and degradation (preventing harmful side effects), to increase drug bioavailability and to release drugs into the cellular nuclei allowing their interaction with DNA.Pubblicazioni consigliate
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