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A. Zarrelli et al. / Bioorg. Med. Chem. Lett. 21 (2011) 4389–4392
lipophilicity is the following: 13 > 8 > 4 ꢁ DHS > 9 > 12 > Sy > 6 >
5 > 11 > 3. From a comparative analysis of the data, it appears that
the observed variations in hydrophilicity do not affect the antiox-
idant activity of the analogues since derivatives at both ends of
the lipophilicity order (i.e., 3, 5, 13 and 8) were more active than
silybin.
the scaffolds 5, 6, 9 and 12, through standard and reliable chemis-
try, are in progress to realize libraries of 23-conjugated silybin and
DHS analogues.
Acknowledgments
It is noteworthy that, as previously mentioned, in these preli-
minary assays here described, mixtures of diastereoisomers and
enantiomers, of silybin and DHS, respectively, have been used
and it cannot be excluded that they might display different activi-
ties. Thus, although considering the difficulties associated to the
This study was supported by M.I.U.R. (PRIN) and A.I.P.R.A.S.
(Associazione Italiana per la Promozione delle Ricerche sull’Ambi-
ente e la Saluta umana). We also thank C.I.M.C.F., Università degli
Studi di Napoli ‘Federico II’, for the NMR, MS facilities.
separation of the diastereoisomeric or enantiomeric mixture,20
a
Supplementary data
future and more detailed study, carried out on separate diastereo-
isomers (or enantiomers), is warranted to complete the character-
ization of the newly synthesized analogues.
Using an in vivo cell-based test, we were also able to evaluate
the concentration inhibiting cell growth by 50% (IC50) for each
tested compound. Cytotoxicity assays were carried out by use of
the MTT test, as previously described.14 Exponentially growing cul-
tures of rat fibroblasts were exposed to increasing concentrations
Supplementary data (experimental procedures, NMR and MS
characterization) associated with this article can be found, in the
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