Alkaloid fagaronine and its interaction with non-canonical DNA structures


                                  Pavel HANNIG^1, Petr TÁBORSKÝ^1


^1Department of Chemistry, Faculty of Science, Masaryk University, Kamenice 5, 625 00 Brno, Czech
Republic


Fagaronine is a rare member of the benzo[c]phenanthridine alkaloid family that can be extracted
from the roots of the Fagara zanthoxyloïdes plant or produced synthetically. Several
benzo[c]phenanthridine alkaloids have already been shown to have a stabilizing effect on
non-canonical structures, in particular on g-quadruplexes, which are secondary DNA structures
occurring on guanine-rich sequences, especially at the ends of telomeres. Increasing the
stabilization of these structures can inhibit DNA replication or transcription, which can result in
a significant reduction in cell division. For this reason, g-quadruplexes have become a popular
target in the search for new anticancer drugs.

In this work, the interactions of fagaronine with parallel, antiparallel and hybrid g-quadruplexes
were measured, some of which occur on human telomeres. We measured that fagaronine significantly
stabilized all 3 types of g-quadruplexes, while parallel G4s were stabilized by up to 30 °C, which
is our highest stabilizing effect measured so far.