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L. Séro et al. / Bioorg. Med. Chem. Lett. 22 (2012) 6716–6720
Acknowledgments
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This work was supported by Grants from la region Pays de la
Loire (PROVASC) and University of Angers. The authors thank B.
Siegler and Dr. I. Freuze for their assistance in NMR spectroscopy
and MS ‘respectively’.
Supplementary data
Supplementary data (synthesis protocols, compounds data and
analytical procedure) associated with this article can be found, in
References and notes
Thiamine ALT-711
PTB
Quercetin
Probe 9
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Tested products
Figure 8. Formation of 1-naphthoic acid from probe 9 (22 mM) and tested product
(10 mM) in DMSO/phosphate buffer pH 7.4 (1:1, 100 L) incubated for 3 h at 37 °C
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fluorescence was observed.
l
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27. Fluorescence quantum yields of 0.04 and 0.13 were determined at 20 °C
respectively for probe 9 and 1-naphthoic acid in EtOH by using anthracene as a
standard.
As shown on Figure 7, in aqueous media, probe 9 is degraded in
1-naphthoic acid but this reaction occurs faster and with a best
yield when an AGEs breaker is added.
As shown on Figures 6 and 7, when this assay to detect AGEs
breakers (10 mM, 1 equiv) using probe 9 (22 mM, 2.2 equiv) was
performed in a mixture DMSO/phosphate buffer pH 7.4, forma-
tion of fluorescent 1-naphthoic acid could be checked after 3 h
at 37 °C using HPLC-UV as well as a fluorescence microplate read-
er (kexc 280 nm). As illustrated by Figure 8, it allows detection of
well-known AGEs breakers such as ALT-711 2 or thiamine and
discriminates AGEs breakers from AGEs inhibitors such as
quercetin.28
Naphthoic acid derivatives, particularly probe 9, described in
this work allow the simple and rapid detection of AGEs breakers
using a 96-well microplate fluorescence assay. To our knowledge,
since the inaugurate publication about AGEs breakers12 whose
activity was demonstrated using HPLC analysis, it is the first pub-
lication about an assay suitable for automated and high through-
put screening of AGEs breakers. Further improvements of this
assay are currently under investigations: one of them consists in
naphthoic acid analogs immobilization on glass support to allow
rinsing steps and avoid fluorescence quenching phenomena due
to evaluated substances.
28. Ferchichi, L.; Derbré, S.; Mahmood, K.; Touré, K.; Guilet, D.; Litaudon, M.; Awang,
K.; Hadi, A. H. A.; Le Ray, A. M.; Richomme, P. Phytochemistry 2012, 78, 98.