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

It is suggested that the widely reported biological synergism of a mixture of DNA-targeting aromatic drug molecules both in vivo and in vitro can be explained, in part, at the molecular level by competition between two basic mechanisms: the ‘interceptor’ (hetero-association between Drug1 and Drug2)...

Full description

Saved in:
Bibliographic Details
Published inBiophysical chemistry Vol. 132; no. 2; pp. 148 - 158
Main Authors Evstigneev, M.P., Lantushenko, A.O., Evstigneev, V.P., Mykhina, Yu. V., Davies, D.B.
Format Journal Article
LanguageEnglish
Published Netherlands Elsevier B.V 01.02.2008
Subjects
Aromatic drugs
Binding Sites
Competitive binding
DNA - metabolism
Drug Synergism
Hetero-association
Interceptor
Methods
Models, Chemical
Models, Theoretical
Protector
Receptors, Drug - metabolism
Aromatic drugs
Hetero-association
Interceptor
Protector
Competitive binding
Online AccessGet full text

Cover

More Information
Summary:It is suggested that the widely reported biological synergism of a mixture of DNA-targeting aromatic drug molecules both in vivo and in vitro can be explained, in part, at the molecular level by competition between two basic mechanisms: the ‘interceptor’ (hetero-association between Drug1 and Drug2) and ‘protector’ mechanisms (complexation of Drug1 and Drug2 on DNA-binding sites). In the present work a complete analytical methodology has been developed to quantify these processes, providing an estimate of the relative importance of the interceptor/protector mechanisms using just a set of equilibrium association constants. The general methodology may be applied to other molecules with receptors for aromatic drugs.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0301-4622
1873-4200
DOI:10.1016/j.bpc.2007.11.001