Synthesis and biological activity of novel bifunctional isoxazolidinyl polycyclic aromatic hydrocarbons

Article abstract of DOI:10.1016/j.bmc.2012.06.035

This paper reports the synthesis and the biological properties of two novel pyrene-bearing isoxazolidinyl derivatives able to exhibit antitumor activity by DNA intercalation. The synthetic approach exploits a consolidated protocol based on 1,3-dipolar cycloaddition reaction. The intercalating properties have been determined by combining electrophoresis studies with molecular docking, while the antitumor activity has been evaluated over five carcinoma cell lines. The obtained compounds show also a good affinity towards silver cations; the presence of a 2-hydroxybenzyl appendage on the isoxazolidine ring ensures a good affinity and selectivity in the binding.

Full text of DOI:10.1016/j.bmc.2012.06.035

Supplementary Material
Synthesis and biological activity of novel bifunctional isoxazolidinyl polycyclic
aromatic hydrocarbons
Antonio Rescifina,a,* Chiara Zagni,a Giovanni Romeob and Salvatore Sortino a,*
aDipartimento di Scienze del Farmaco, Università di Catania, Viale Andrea Doria 6, Catania 95125, Italy
bDipartimento Farmaco-Chimico, Università di Messina, Viale SS. Annunziata, Messina 98168, Italy
NOE assignments for compounds 1
For cis compound 1a, irradiation of H5 gave a small enhancement of H3 (0.7%) that directly prove
the stereochemical arrangement. For trans compound 1b, irradiation of H5 produced an
enhancement of only H4a (3.7%) whereas irradiation of H3 produced a good enhancement of only
H4b (7.2%). Conversely, irradiation of H4a and H4b gives rise to positive NOE effects for H5 (7.7%)
and H3 (8.6%), respectively.
. – .
3 7 7 7%
R1
R1
H4
a
H4b
H5
H3
H3
H5
R3
.
0 7%
. – .
7 2 8 6
%
N
N
R2
R2
R3
O
O
a
1
1b
Figure. S1. Selected NOEs for compounds 1a,b.
Unwinding assay
Figure. S2. Inhibition of topoisomerase I-induced DNA relaxation by compound 1a at 0.1, 1, 10 ,20, 30 and 40 µM.
*
Corresponding author. Tel.: +39 095 7385014; Fax: +39 06 233208980.
e-mail address: arescifina@unict.it (A. Rescifina).
S1