Complexation of anthracycline drugs with DNA in the presence of caffeine.
The competitive binding of anthracycline antitumour drugs, [daunomycin (DAU), doxorubicin (DOX) or nogalamycin (NOG)], with caffeine (CAF) to a model DNA oligomer has been investigated by 500 MHz 1H NMR spectroscopy under physiological solution conditions. The method depends on the stepwise analysis of one-component (self-association), two-component (hetero-association and DNA complexation) and three-component interactions, in order to de-convolute the overall binding of the anthracycline antibiotic and CAF to DNA into two competing processes, viz. hetero-association of the antibiotic-CAF ('interceptor' action of CAF) and CAF-DNA complexation ('protector' action of CAF). It is found that the complexation of DAU with DNA in the presence of CAF is mainly affected by the CAF-DNA complexation, whereas the binding of either DOX or NOG to DNA is affected approximately equally by both the CAF-DNA complexation and CAF-antibiotic hetero-association. Quantitative evaluation of the three-component mixture of drug-CAF-DNA has enabled the proportion of the antibiotic displaced from DNA on addition of CAF to be calculated over a large range of CAF concentration, which may provide a quantitative basis for the change in anthracycline-related toxicity on addition of CAF.
Evstigneev
M P
MP
Department of Physics, Sevastopol National Technical University, Sevastopol 99053, Crimea, Ukraine. max_evstigneev@mail.ru
Khomich
V V
VV
Davies
D B
DB
D018943:Anthracyclines / Q000737:chemistry / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001667:Binding, Competitive; D002021:Buffers; D002110:Caffeine / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D003630:Daunorubicin / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D004357:Drug Synergism; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D015233:Models, Statistical; D009621:Nogalamycin / Q000494:pharmacology; D013696:Temperature
D018943:Anthracyclines; D000900:Anti-Bacterial Agents; D002021:Buffers; D000697:Central Nervous System Stimulants; D002110:Caffeine; D004317:Doxorubicin; D004247:DNA; D009621:Nogalamycin; D003630:Daunorubicin