Analyst (Cambridge UK) 2009-09-01

Molecular spectroscopy and chemometrics: an analytical study of synergistic effects of drugs--interaction between fluoroquinolones and DNA.

Yongnian Ni, Shan Du, Serge Kokot

文献索引：Analyst 134(9) , 1840-7, (2009)

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摘要

Three commonly used fluoroquinolone antibiotics (norfloxacin (NFX), ofloxacin (OFX) and lomefloxacin (LMFX)) were used as examples of molecules which can interact with a biomacromolecule, such as DNA, separately or in a mixture. Such interactions were investigated with the use of UV and Synchronous Fluorescence Spectroscopy (SFS). Equilibrium binding (K(ap)) and Stern-Volmer equilibrium (K(SV)) constants were extracted from these two types of spectra from interactions of DNA with single fluoroquinolones. The values of these equilibrium constants were relatively low, and this suggested that the DNA groove was the likely binding site. The complex SFS profiles obtained from the interactions of the DNA with the drug analyte mixtures were resolved, with the use of the curve resolution method, parallel factor (PARAFAC) analysis, into spectra of individual drugs. From these spectra, the (K(SV)) values for the individual analytes in the mixture were obtained. Also extracted were the concentrations of the individual quinolones as a function of concentration of the DNA. From a comparison of the equilibrium constants for the individual drug-DNA interaction with those obtained from the interaction with the drugs in a mixture, it was found that the binding strength of a single analyte to DNA was LMFX > NFX > OFX, but when the drug mixture was involved, this order was reversed. Importantly, it was also found that the equilibrium uptake of the drugs OFX and NFX was higher than from single drug-DNA experiments; the concentrations of LMFX did not change significantly. These observations collectively suggested that the binding of NFX and OFX to DNA is synergistically affected and that they probably share similar binding sites, while the LMFX was bound to a different site. This new important qualitative and quantitative information, which can now act as a springboard for more complex and deeper studies of the apparent synergistic effects of drug interactions with biomacromolecules, could only be obtained by the combination of three-way array SFS measurements and their interpretation by a chemometrics curve resolution method such as PARAFAC.