Quantitation of the molecular mechanisms of biological synergism in a mixture of DNA-acting aromatic drugs

Evstigneev, Maxim P.; Лантушенко, А. О.; Evstigneev, V. P.; Mykhina, Yu.V.; Davies, David B.

doi:10.1016/j.bpc.2007.11.001

Cited by 21 publications

(61 citation statements)

References 68 publications

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“…These features enable us to draw a parallel with the well-investigated drug-xanthine systems (Buchelnikov et al 2012;Evstigneev et al 2006Evstigneev et al , 2008Evstigneev et al , 2011Evstign eev 2010Evstign eev , 2013Goluriski et al 2013;Larsen et al 1996;Piosik et al 2010;Traganos et al 1991;Woziwodzka et al 2011), for which similar effects are observed on joint in vitro action of aromatic BACs. Of particular importance here is that in the drug-xanthine systems, the operation of the interceptor mechanism (i.e., the drugxanthine hetero-association) can be considered as widely accepted.…”

Section: Drug Action In the Presence Of C6fl Fullerenementioning

confidence: 93%

“…Unfortunately, identification of the role of the interceptor mechanism directly at the cellular level is not possible, and in similar works available in the lit erature, the conclusions about its significance are com monly made on the basis of either the fact of an effective drug-interceptor hetero-association (Piosik et al 2010;Traganos et al 1991;Woziwodzka et al 2011), or the ability to describe in vitro data within the framework of the theory of interceptor/protector action (Buchelnikov et al 2012;Evstigneev et al 2008Evstigneev et al , 2011Evstigneev 2010). The existence of an effective hetero-association in the drug-fullerene systems has been shown previously , and the degree of correspond ence of the parameters measured in the present work (HGQ, ENN) with the theory of interceptor/protector action was investigated in order to gain further under standing of the role of the interceptor mechanism in the biological effects observed (see Fig.…”

Section: Drug Action In the Presence Of C6fl Fullerenementioning

confidence: 99%

“…Taking into account that C6fl fullerene has a saturated 7r-electron system and therefore can form com plexes with aromatic DNA intercalators, including antineo plastic antibiotics and mutagens Evstigneev et al 2013;Mchedlov-Petrossyan et al 2001), it was suggested that a non-covalent complexation in the 'drug-fullerene' system (also referred to as hetero-association) is a key mechanism causing the observed biological synergism . It has been known for quite a long time and so far been observed in proliferat ing cells or bacterial systems [see for review (Evstigneev et al 2008;Evstigneev 2010Evstigneev , 2013] that hetero-association regulates the action of the biologically active compounds during simultaneous administration of combinations of dif ferent aromatic molecules, one of which is the main drug of interest, and the other one is an interceptor molecule. This phenomenon is referred to as an 'interceptor' mechanism.…”

Section: Introductionmentioning

confidence: 99%

“…However, the study of such a mechanism is complicated by possible influence from other molecular processes, one of which is most often referred to as a 'protector' mechanism, i.e., the drug/interceptor competition for the binding sites on DNA (Buchelnikov et al 2012;Evstigneev 2010Evstigneev , 2013Evstigneev et al 2011;Goluriski et al 2013). Investigation of the interceptor and protector mechanisms for DNA-bind ing drugs used in combination is the subject of the theory of interceptor/protector action (Buchelnikov et al 2012;Evstigneev et al 2008Evstigneev et al , 2011Evstigneev 2010). Unfortu nately, the applicability of the protector mechanism within the system containing C6fl fullerene cannot be estimated on the basis of the currently available literature data.…”

Section: Introductionmentioning

confidence: 99%

“…These drugs form stable non-cova lent complexes with C6fl fullerene Evstigneev et al 2013) and were previously characterized as the ligands that follow the mechanism of interceptor/ protector action when used in combination with various types of aromatic interceptor molecules (Buchelnikov et al 2012;Evstigneev et al 2006Evstigneev et al , 2008Evstigneev 2010Evstigneev , 2013Larsen et al 1996;Piosik et al 2010;Traganos et al 1991).…”

Section: Introductionmentioning

confidence: 99%

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Interceptor effect of C60 fullerene on the in vitro action of aromatic drug molecules

et al. 2014

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C60 fullerenes are spherical molecules com posed purely of carbon atoms. They inspire a particularly strong scientific interest because of their specific physico chemical properties and potential medical and nanotech nological applications. In this work we are focusing on studying the influence of the pristine C60 fullerene on bio logical activity of some aromatic drug molecules in human buccal epithelial cells. Assessment of the heterochromatin structure in the cell nucleus as well as the barrier function of the cell membrane was performed. The methods of cell microelectrophoresis and atomic force microscopy were also applied. A concentration-dependent restoration of the functional activity of the cellular nucleus after exposure to DNA-binding drugs (doxorubicin, proflavine and ethidium bromide) has been observed in human buccal epithelial cells upon addition of C60 fullerene at a concentration of -1СГ5 M. The results were shown to follow the framework of interceptor/protector action theory, assuming that noncovalent complexation between C60 fullerene and the drugs (i.e., hetero-association) is the major process responsible for the observed biological effects. An independent con firmation of this hypothesis was obtained via investigation of the cellular response of buccal epithelium to the coad ministration of the aromatic drugs and caffeine, and it is based on the well-established role of hetero-association in drug-caffeine systems. The results indicate that C60 fuller ene may reverse the effects caused by the aromatic drugs, thereby pointing out the potential possibility of the use of aromatic drugs in combination with C60 fullerene for regu lation of their medico-biological action.

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Section: Drug Action In the Presence Of C6fl Fullerenementioning

confidence: 93%

Section: Drug Action In the Presence Of C6fl Fullerenementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Interceptor effect of C60 fullerene on the in vitro action of aromatic drug molecules

et al. 2014

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Quantification of the interceptor action of caffeine on the in vitro biological effect of the anti-tumour agent topotecan

et al. 2011

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Using published in vitro data on the dependence of the percentage of apoptosis induced by the anti-cancer drug topotecan in a leukaemia cell line on the concentration of added caffeine, and a general model of competitive binding in a system containing two aromatic drugs and DNA, it has been shown to be possible to quantify the relative change in the biological effect just using a set of component concentrations and equilibrium constants of the complexation of the drugs. It is also proposed that a general model of competitive binding and parameterization of that model may potentially be applied to any system of DNA-targeting aromatic drugs under in vitro conditions. The main reasons underpinning the proposal are the general feature of the complexation of aromatic drugs with DNA and their interaction in physiological media via hetero-association.

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General analysis of competitive binding in drug–interceptor–DNA systems

et al. 2012

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A general model of competitive binding in drug-interceptor-DNA systems has been developed in order to quantify both the interceptor and protector mechanisms. The model involves full parameterization of the basic equations governing the mutual competition between drugs binding to DNA and incorporates as partial cases various similar models existing in the literature. The generality of the model results from strict accounting of the statistical effects of the binding of the drug and interceptor with DNA according to the McGhee-von Hippel formalism, and to the strict treatment of hetero-association between the drug and interceptor, which includes formation of all possible types of self- and hetero-complexes in solution. Indirect experimental evidence is provided for the importance of the protector mechanism in drug-caffeine-DNA systems, which is sometimes ignored in the literature because of the small magnitude of the CAF-DNA binding constant.

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Quantitation of the molecular mechanisms of biological synergism in a mixture of DNA-acting aromatic drugs

Cited by 21 publications

References 68 publications

Interceptor effect of C60 fullerene on the in vitro action of aromatic drug molecules

Interceptor effect of C60 fullerene on the in vitro action of aromatic drug molecules

Quantification of the interceptor action of caffeine on the in vitro biological effect of the anti-tumour agent topotecan

General analysis of competitive binding in drug–interceptor–DNA systems

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