S. Wu et al. / Bioorg. Med. Chem. Lett. 14 (2004) 2575–2577
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Figure 3. Cleavage of supercoiled pBR322 DNA by porphyrins 3, 4,
and 7. Reaction mixtures (10 lL) contained 0.15 lg of plasmid DNA.
Lane 1: DNA alone; lane 2: DNA þ hm (20 min); lane 3: DNA þ 3%
DMF; lane 4: DNA þ 3% DMF þ hm (20 min); lane 5: DNA þ com-
pound 3 (6 lM); lane 6: DNA þ compound 3 (6 lM) þ hm (20 min); lane
7: DNA þ compound
4
(6 lM); lane 8: DNA þ compound
4
(6 lM) þ hm (20 min); lane 9: DNA þ compound 7 (6 lM); lane 10:
DNA þ compound 7 (6 lM) þ hm (20 min).
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5. Selected data: compound 4 1H NMR dH([2H6]-DMSO,
300 MHz): 9.91 (s, 4H), 9.45 (m, 4H), 9.00 (m, 8H), 5.12 (m,
4H), 4.73 (m, 6H), 2.05 (m, 6H), ꢀ2.95 (s, 2H); dC([2H6]-
DMSO, 75 MHz): 158.3, 144.6, 132.8, 132.3, 130.8, 124.1,
113.9, 28.5, 26.9, 24.1; UV–vis kmax (DMF, nm, log e): 422.0
(5.11), 518.0 (3.90), 556.0 (3.69), 596.0 (3.24), 654.0 (3.80);
HRMS (ESI, m=z): calcd for C36H34N6[(Mþꢀ2I)/2]:
275.1417 found: 275.1417.
Peripheral substituent effects of compounds 3, 4, and 7
were reflected by the result of cytotoxic ability to THP-1
tumor cells. A MTT assay was performed to determine
THP-1 cell viability.9 Cytotoxic data were expressed as
IC50 values (the concentration of the test agent inducing
50% reduction in cell numbers compared with control
cultures). The IC50 value of compound 3 was 0.11 nM,
compound 4 was 32 nM and compound 7 was 12 nM. It
suggested that structure relationship of porphyrins
could affect their interactions with DNA and finally lead
the difference for cytotoxicity to tumor cells. Further
peripheral substituent effects, for example, electronic
effects and steric effects, on porphyrins to DNA and
tumor cells are being investigated.
1
Compound 7 H NMR dH([2H6]-DMSO, 300 MHz): 10.39
(s, 2H), 9.48 (m, 4H), 9.06 (m, 4H), 4.79 (s, 6H), 4.10 (m,
8H), 2.54 (s, 12H), 1.76 (t, J1 ¼ J2 ¼ 3:3 Hz, 12H), ꢀ2.50 (s,
2H); dC([2H6]-DMSO, 75 MHz): 157.6, 146.2, 144.8, 142.8,
141.0, 140.9, 134.8, 131.5, 112.4, 97.7, 19.0, 17.6, 17.5, 15.4;
UV–vis kmax (DMF, nm, log e): 410.5 (5.08), 508.0 (4.12),
543.5 (3.79), 577 (3.75), 628.5 (3.46); HRMS (ESI, m=z):
calcd for C44H50N6[(Mþꢀ2I)/2]: 331.2043, found: 331.2044.
6. (a) Dougherty, T. J. J. Natl. Cancer Inst. 1998, 90, 889; (b)
Sternberg, E. D.; Dolphin, D.; Bruckner, C. Tetrahedron
1998, 54, 4151; (c) Bonnett, R. Chemical Aspects of
Photodynamic Therapy; Gordon and Breach Science:
Amsterdam, 2000.
7. (a) Ishikawa, Y.; Yamakawa, N.; Uno, T. Bioorg. Med.
Chem. 2002, 10, 1953; (b) Oda, K.; Ogura, S.; Okura, I.
J. Photochem. Photobiol. B 2000, 59, 20; (c) Kochevar, I. E.;
Redmond, R. W. Methods Enzymol. 2000, 319, 20; (d)
Michelsen, M.; Kliesch, H.; Wohrle, D. Photochem. Pho-
tobiol. 1996, 64, 694.
Acknowledgements
This work was supported by grants from the Trans-
Century Training Programme Foundation for the Tal-
ents by the Ministry of Education of China and the
Scientific Research Foundation for the Returned Over-
seas Chinese Scholars, Ministry of Education of China.
We appreciate one referee for his critical comments on
this manuscript.
8. (a) Fiel, R. J. J. Biomol. Struct. Dyn. 1989, 6, 1259; (b)
Kubat, P.; Lang, K.; Anzenbacher, P., Jr.; Jursikova, K.;
Kral, V.; Ehrenberg, B. J. Chem. Soc., Perkin. 1 2000, 6,
933.
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