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Fig. 4 Candida albicans antimicrobial assay: the activity of r3 was
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(a) sterile disk with r3 (not irradiated); (b) positive azapentamidine
control; (c) UV-irradiated r3; (d) commercial antibiotic (clotrimazole);
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preferred AAATTT binding site (lexc Z 360 nm) triggered a
progressive fluorescence emission enhancement, which must
be attributed to the binding of the light-released DAPI to the
DNA (Fig. S4, ESIw).
At this point we were then challenged to demonstrate whether
our strategy would allow triggering of a relevant biological activity
with light. Given that the Nvoc protection is effective for DNA
binding inhibition, and considering that the hydrophobic charac-
teristics of this protecting group might help for in vivo experiments,
we decided to prepare the bis-Nvoc-azapentamidine derivative r3,
and assay an antifungal activity. Therefore we ran agar diffusion
growth inhibitory assays for Candida albicans, a fungus respon-
sible of many opportunistic infections in humans. Gratifyingly,
while the fungus growth was unaffected by the caged azapenta-
midine r3, it was readily inhibited by incubation with irradiated
samples of r3. Control experiments with 1a and with the
commercial antifungal clotrimazole, as well as negative controls
with buffer and UV light, confirmed r3 as an efficient light-
activatable antifungal agent (Fig. 4).
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In summary, we have implemented a strategy that allows the
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In the case of the pentamidine, we have also demonstrated
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This work was funded by the Spanish grants CTQ2009-
14431/BQU, SAF2010-20822-C02, Consolider Ingenio 2010
CSD2007-00006 and the ERDF and the Xunta de Galicia
INCITE09 209 084PR, INCITE09 209 122PR, GRC2010/12,
PGIDIT08CSA-047209PR. M. I. S. and O. V. thank the
Spanish ministry for their PhD fellowships.
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c
This journal is The Royal Society of Chemistry 2011
Chem. Commun., 2011, 47, 11107–11109 11109