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has been expressed by IC50 values, that is, by molar con-
References and notes
centration of the compounds causing 50% decrease in
the oxygen evolution relative to the untreated control.
The comparable IC50 value for a selective herbicide
3-(3,4-dichlorophenyl)-1,1-dimethylurea, DCMU (DIU-
RON), was about 1.9 lmol/L. The results are summa-
rized in Table 2.
1. Anzali, S.; Barnickel, G.; Cezanne, B.; Krug, M.; Filim-
onov, D.; Poroikov, V. J. Med. Chem. 2001, 44, 2432.
2. Kos, A.; PASS Prediction of Activity Spectra for Sub-
3. Roth, H. J.; Fenner, H. In Arzneistoffe, 3rd ed.; Deutscher
Apotheker Verlag: Stuttgart, 2000; pp 51–114.
4. Mekouar, K.; Mouscadet, J. F.; Desmaele, D.; Subra, F.;
Leh, H.; Savoure, D.; Auclair, C.; d’Angelo, J. J. Med.
Chem. 1998, 41, 2846.
5. Zouhiri, F.; Danet, M.; Bernard, C.; Normand-Bayle, M.;
Mouscadet, J. F.; Leh, H.; Thomas, C. M.; Mbemba, G.;
d’Angelo, J.; Desmaele, D. Tetrahedron Lett. 2005, 46,
2201.
6. Pommier, Y.; Johnson, A. A.; Marchand, C. Nat. Rev.
Drug. Discov. 2005, 4, 236.
7. Polanski, J.; Zouhiri, F.; Jeanson, L.; Desmaele, D.;
d’Angelo, J.; Mouscadet, J.; Gieleciak, R.; Gasteiger, J.;
Bret, M. L. J. Med. Chem. 2002, 45, 4647.
8. Musiol, R.; Jampilek, J.; Buchta, V.; Silva, L.; Niedbala,
H.; Podeszwa, B.; Palka, A.; Majerz-Maniecka, K.;
Oleksyn, B.; Polanski, J. Bioorg. Med. Chem. 2006, 14,
3592.
9. Jampilek, J.; Dolezal, M.; Kunes, J.; Buchta, V.; Kralova,
K. Med. Chem. 2005, 1, 591.
10. Polanski, J.; Niedbala, H.; Musiol, R.; Tabak, D.;
Podeszwa, B.; Gieleciak, R.; Bak, A.; Palka, A.; Magdz-
iarz, T. Acta Poloniae Pharm. Drug Res. 2004, 61, 3.
11. Musiol, R.; Niedbala, H.; Polanski, J. Monatsh. Chem.
2006, 137, 1211.
12. Majerz-Maniecka, K. A.; Musiol, R.; Nitek, W.; Oleksyn,
B. J.; Polanski, J. Bioorg. Med. Chem. Lett. 2006, 16, 1005.
13. Pliska, V. In Lipophilicity in Drug Action and Toxicology;
Pliska, V., Testa, B., van der Waterbeemd, H., Eds.;
Wiley-VCH, 1996; pp 1–6.
4.7.2. Study of chlorophyll content reduction in C.
vulgaris Beij. The green algae C. vulgaris Beij. was
cultivated statically at room temperature according
to Kralova et al.31 (photoperiod 16 h light/8 h dark;
photosynthetic active radiation 80 lmol/m2 s, pH
7.2). The effect of the compounds on algal chloro-
phyll (Chl) content was determined after 7-day culti-
vation in the presence of the tested compounds. The
Chl content in the algal suspension was determined
spectrophotometrically (Kontron Uvikon 800, Kon-
tron, Muenchen, Germany) after extraction into
methanol according to Wellburn.32 The Chl content
in the suspensions at the beginning of the cultivation
was 0.01 mg/L. Because of the low solubility of the
studied compounds in water, these were dissolved in
DMSO. DMSO concentration in the algal suspen-
sions did not exceed 0.25% and the control samples
contained the same DMSO amount as the suspen-
sions treated with the tested compounds. The antial-
gal activity of the compounds was expressed as
IC50. The comparable IC50 value for a selective her-
bicide DCMU was about 7.3 lmol/L. The results
are summarized in Table 2.
4.7.3. Antiproliferative activity. The human SK-N-MC
neuroepithelioma cell line was seeded in 96-well micro-
titer plates at 1.5 · 104 cells/well in the medium con-
taining unlabeled human diferric transferrin (0.06 mg/
mL) and compounds at a range of concentrations
(0.0–6.25 lmol). Control samples contained the medi-
um with diferric transferrin (0.06 mg/mL) without any
ligands. The cells were incubated at 37 ꢁC in a humid-
ified atmosphere containing 5% CO2 and 95% air for
96 h. After the incubation, 10 lL (5 mg/mL) of 1-(4,5-
dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium (MTT)
was added to each well and further incubated at
37 ꢁC for 2 h. After solubilization of the cells with
100 lL of 10% SDS-50% isobutanol in 0.01 mol HCl,
the plates were read at 570 nm using a scanning mul-
ti-well spectrophotometer. The inhibitory concentration
(IC50) was defined as the concentration necessary to re-
duce the absorbance to 50% of the untreated control.
The comparable IC50 value for the standard chelator
3-aminopyridine-2-carbaldehyde-thiosemicarbazone
(triapine) was about 0.31 lmol/L. The results are
shown in Table 2.
14. Niewiadomy, A.; Matysiak, J.; Zabinska, A.; Rozylo, J.
K.; Senczyna, B.; Jozwiak, K. J. Chromatogr. A 1998, 828,
431.
15. VandeWaterbeemd, H.; Smith, D. A.; Jones, B. C. J.
Comp.-Aided Mol. Des. 2001, 15, 273.
16. Colmenarejo, G.; Alvarez-Pedragilo, A.; Lavandera, J.-L.
J. Med. Chem. 2001, 44, 4370.
17. Musiol, R.; Jampilek, J.; Podeszwa, B.; Finster, J.; Tabak,
D.; Polanski, J. Structure–lipophilicity relationship in series
of quinoline derivatives. 18th International Conference on
Physical Organic Chemistry, Warsaw, 20–25, August,
2006, 76, PII-16.
18. Pollien, P.; Roberts, D. J. Chromatogr. A 1999, 864, 183.
19. Palmer, M. H. In The Structure and Reactions of Hetero-
cyclic Compounds; Edward Arnold Publisher Ltd: Lon-
don, 1967; pp 105–144.
20. Jegerschold, C.; Styring, S. FEBS Lett. 1991, 280, 87.
21. Dolezal, M.; Kralova, K.; Sersen, F.; Miletin, M. Folia
Pharm. Univ. Carol. 2001, 26, 13.
22. Finch, R. A.; Liu, M.; Grill, S. P.; Rose, W. C.; Loomis,
R.; Vasquez, K. M.; Cheng, Y.; Sartorelli, A. C. Biochem.
Pharmacol. 2000, 59, 983.
23. Seradj, H.; Cai, W.; Erasga, N. O.; Chenault, D. V.;
Knuckles, K. A.; Ragains, J. R.; Behforouz, M. Org. Lett.
2004, 6, 473.
24. Behforouz, M.; Haddad, J.; Cai, W.; Arnold, M. B.;
Mohammadi, F.; Sousa, A. C.; Horn, M. A. J. Org. Chem.
1996, 61, 6552.
25. Albert, A.; Magrath, D. Biochem. J. 1947, 41, 534.
26. Musiol, R.; Tyman-Szram, B.; Polanski, J. J. Chem. Educ.
2006, 83, 632.
Acknowledgments
This study was supported by the Slovak Scientific Grant
Agency VEGA No. 1/3571/06, by the Ministry of Edu-
cation of the Czech Republic MSM 6215712403, and
in synthetic part by a grant from KBN Warsaw:
3T09A 01127.
27. Santagati, N. A.; Bousquet, E.; Spadaro, A.; Ronsisvalle,
G. Farmaco 1999, 54, 780.