Abstract:
Human DNA Topoisomérase I (topo I) is the tar
get of several drugs commonly used in
cancer chemotherapy. These drugs induce topo-DNA co
mplexes that eventually trigger cell
death. Several flavonoides have been shown as inhib
itors of topo I, having an anticancer
activity.
Using the methods of molecular modeling in pa
rticularl the docking by the Surflex program,
we theoretically evaluated the affinity of four fla
vonoids: myricetin, fisetin, quercetin and
apigenin, presented in recent studies as inhibitors
of topo I. Myricetin with the lowest IC
50
(11.1 ± 2.0 μ M) gave the best affinity (7.01 M
-1
). For the development
in silico
of novel
molecules most powerful myricetin, we have made sev
eral substitutions. Replacing the hydroxyl
group carried by the carbone C3 ́ of the myricetin b
y an alcoholic group CH
2
OH significantly
improves the affinity increases from 7.01 M
-1
to 8.79 M
-1
.
The application of the rule of Lipinski inform
s in a positive way about the ADME properties
of this new molecule that is as an inhibitor potent
ially more active than myricetin.
