XXII. BIOCHEMICKÝ ZJAZD - Jesseniova lekárska fakulta

Lectures
AcrIDINES – USEfUL MUTaGENS
Helena Paulíková
Department of Biochemistry and Microbiology, Faculty of Chemical and Food
Technology, Slovak Technical University, SK-81237 Bratislava
Acridine based compounds comprise of an important class of DNA-intercalating anticancer
drugs, and are structurally characterised by the presence of a planar chromophore
capable of intercalation into DNA. However acridines are a double-edged sword, they
are known as substances cause mutation and cancer. Most notable among their mutagenic
effects is the induction of frameshift mutations. In spite of their mutagenicity,
DNA affinity makes them attractive for the design of antitumor drug targeting DNA. Four
new classes of acridine derivatives have been investigated by our research group and
their anticancer potential has been assessed. Intercalation into DNA was confirmed by
a variety of spectroscopic and electrophoresis techniques and anti-proliferative activity
against three tumor cell lines (L1210, HL-60; A2780) was observed. The mechanism of
antitumor activity of acridines involves intercalator-dependent formation of irreparable
DNA double or single strand breaks arising from the inhibiting of DNA topoisomerases.
Although acridines are also known as mutagens, the data obtained from the literature
and our results showed that not all acridine intercalators are mutagens and it seems that
the presence of electrophilic functional groups is nescessary for mutagenicity.
Acknowledgements: Supported by Slovak Grant Agency, grants No 1/0097/10 and
1/0053/08.
86 XXII. Biochemistry Congress, Martin