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) 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.
Evstigneev
M P
MP
Department of Physics, Sevastopol National Technical University, Sevastopol, Crimea, Ukraine. max-evstigneev@mail.ru
Lantushenko
A O
AO
Evstigneev
V P
VP
Mykhina
Yu V
YV
Davies
D B
DB
D001665:Binding Sites; D004247:DNA / Q000378:metabolism*; D004357:Drug Synergism; D008722:Methods; D008956:Models, Chemical; D008962:Models, Theoretical; D011955:Receptors, Drug / Q000378:metabolism
D011955:Receptors, Drug; D004247:DNA