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Conjugates 3 and 4 were prepared in good yields and were
thoroughly characterized. On the basis of previously reported
immunostimulatory activities of a pristine Tb, we evaluated immu-
nobiological potency of the prepared Tb–porphyrin conjugates in
rat macrophages as a measure of NO production. The more pro-
nounced NO production was induced by Tb-derivative 1d than by
Tb–porphyrin conjugates in comparison with Tb. Moreover, these
compounds did not exhibit cytotoxic effect in vitro in a number
of model cell lines, such as primary macrophages, LNCaP, MCF-7,
U-2 OS, and MiaPaCa-2. The IC50 value was not reached up to 50
verteporfin in age-related macular degeneration:
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Prodrugs: design and clinical applications. Nat Rev Drug Discov
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10] Di Stasio B, Frochot C, Dumas D. The 2-aminoglucosamide motif improves
cellular uptake and photodynamic activity of tetraphenylporphyrin. Eur J Med
Chem 2005;40:1111–22.
[11] Sibrian-Vazquez M, Nesterova IV, Jensen TJ, Vicente MGH. Mitochondria
targeting by guanidine- and biguanidine-porphyrin photosensitizers.
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12] Sibrian-Vazquez M, Jensen TJ, Fronczek FR, Hammer RP, Vicente MGH.
Synthesis and characterization of positively charged porphyrin–peptide
conjugates. Bioconjug Chem 2005;16:852–63.
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derivatives of tetraphenyl porphyrin: photophysical characterization, self-
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lM concentration of the tested compounds. Utilizing the inherent
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fluorescence properties of porphyrins, we examined intracellular
localization of the Tb–porphyrin conjugates in living cells in real
time. Interestingly, the compounds 3 and 4 localized in mitochon-
[
[
dria and lysosomes of the model cancer cell lines in 5 lM concen-
tration already after 2 h. Further biological analysis is needed for
differentiation between physico-chemical properties and possible
immunobiological effect (NO production) of porphyrin and its
conjugates in macrophages.
aggregation and membrane binding.
998;44:216–24.
J
Photochem Photobiol
B
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14] Sibrian-Vazquez M, Jensen TJ, Vicente MGH. Influence of the number and
distribution of NLS peptides on the photosensitizing activity of multimeric
porphyrin-NLS. Org Biomol Chem 2010;8:1160–72.
15] Sadler S, Persons KS, Jones GB, Ray R. Internalization of
a C17a-
alkynylestradiol-porphyrin conjugate into estrogen receptor positive MCF-7
breast cancer cells. Bioorg Med Chem Lett 2011;21:4638–41.
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Conflict of interest
16] Shieh M-J, Peng C-L, Lou P-J, Chiu C-H, Tsai T-Y, Hsu C-Y, et al. Non-toxic
phototriggered gene transfection by PAMAM-porphyrin conjugates. J Control
Release 2008;129:200–6.
The authors declare no competing financial interest.
[
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17] Sibrian-Vazquez M, Jensen TJ, Vicente MGH. Porphyrin-retinamides: synthesis
Acknowledgements
and cellular studies. Bioconjug Chem 2007;18:1185–93.
18] Kmoní cˇ ková E, Harmatha J, Voká cˇ K, Kostecká P, Farghali H, Zídek Z.
Sesquiterpene lactone trilobolide activates production of interferon-gamma
and nitric oxide. Fitoterapia 2010;81:1213–9.
19] Winther A-ML, Liu H, Sonntag Y, Olesen C, Le MM, Soehoel H, et al. Critical
roles of hydrophobicity and orientation of side chains for inactivation of
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This work was supported by Czech Science Foundation (GA Cˇ R)
303/14/ 04329-S and MSMT No. 20/2014 and ED2.1.00/3.0076.
We thank Dr. Juraj Harmatha from IOCB AVCR (Prague) for gener-
ous providing of trilobolide for this study.
[
2+
sarcoplasmic reticulum Ca -ATPase with thapsigargin and thapsigargin
analogs. J Biol Chem 2010;285:28883–92.
[
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20] Huisgen R. Kinetics and mechanism of 1,3-dipolar cycloadditions. Angew
Chem Int Ed 1963;75:633–45.
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Chem Soc 2011:241.
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oxidation of limonene by amphiphilized metalloporphyrins in micellar media.
Langmuir 2001;17:7198–203.
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cycloaddition of organic azides and 1-iodoalkynes. Angew Chem Int Ed
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Appendix A. Supplementary data
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