XXII. BIOCHEMICKÝ ZJAZD - Jesseniova lekárska fakulta

Posters
85.
DNA BINDING STUDY of 9-OXO-9,10-DIHYDroacrIDINcarBOXYHYDraZIDES
as POTENT TOPOISOMEraSE I INHIBITOrs
Danica Sabolová, Lucia Krajňáková, Jana Plšíková and Mária Kožurková
Department of Biochemistry, Institute of Chemistry, Faculty of Science,
P.J. Šafárik University, Moyzesova 11, SK-04167 Košice
DNA, the basic genetic material, is one of the most enigmatic biomolecules and efforts
to understand the subtleties of its behaviour from a structural and energetic perspective
have not yet been fully rewarded. The pivotal role played by DNA in the synthesis
of proteins as well as its own replication makes it an extremely important potential
target for drugs, especially for anticancer, antibiotic and antiviral action. Regions of DNA
involved in vital processes like origin of replication, promotion of transcription etc. are
of particular interest as targets for such drugs.
In this work, the interactions of acridone derivates 9-oxo-9,10-dihydroacridine-carbohydrazides
with DNA were studied by a variety of spectroscopic techniques including
UV-Vis spectrophotometry, fluorimetric titrations and circular dichroism. From spectrofluorimetric
titrations the binding constants for DNA - drug complexes were determined
(K= 1.2 × 10 5 M -1 – 5.1 × 10 5 M -1 ). The effect of investigated compounds on the thermal
denaturation profiles of calf thymus DNA were also studied. By electrophoretic methods
was determined, that the new drugs were able to inhibit the topoisomerase I.
Acknowledgements: This work was supported by the Slovak Grant Agency VEGA, No.
1/0053/08 and 1/0097/10.
208 XXII. Biochemistry Congress, Martin