[Interaction of the antineoplastic agent mitoxantrone with double-stranded nucleic acids].
The binding of mitoxantrone with double-helical nucleic acids was investigated by the methods of isothermal microcalorimetry, circular dichroism and absorption at the ionic strength mu = 0.11 and 0.011 M NaCl at temperature region of 30 divided by 60 degrees C. The investigation shows, that at mu = 0.11 M NaCl mitoxantrone interacts with double-helical nucleic acids in one way only. For such conditions using spectrophotometric titration data Scatchard plots for the binding of mitoxantrone with double-helical nucleic acids were constructed. The calculations show that the saturation stoichiometry is one mitoxantrone molecule per 2 divided by 3 base pairs DNA and 6 divided by 8 base pairs RNA. The dependence of binding constant from GC-content is observed. It is shown that the binding enthalpy of mitoxantrone with DNA and RNA increases linearly and reaches -(3.0 +/- 0.5) kkal per 1 mol mitoxantrone. It is shown that a binding mitoxantrone with double-helical nucleic acids, besides the intercalation of rings, a determinate contribution in the binding is given also by electrostatic interaction of side chains mitoxantrone with nucleic acids.
Babaian
Iu S
IuS
Manzini
G
G
D000818:Animals; D002417:Cattle; D002942:Circular Dichroism; D004247:DNA / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008942:Mitoxantrone / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D012330:RNA, Double-Stranded / Q000187:drug effects / Q000378:metabolism*; D013816:Thermodynamics; D013950:Thymus Gland / Q000378:metabolism
D012330:RNA, Double-Stranded; D004247:DNA; D008942:Mitoxantrone
Vzaimodeĭstvie protivoopukholevogo soedineniia mitoksantrona s dvuspiral'nymi nukleinovymi kislotami.