3
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2. Pandey, R. K.; Zengh, G.; Kadish, K. M.; Smith, K. M.; Guilard, R. The Porphyrin
Table 1
Cytotoxicity of the porphyrins against A549 cells in vitro
Handbook; Academic Press: San Diego, 2000. p 157.
Josefsen, L. V.; Boyle, R. W. Met-Based Drugs 2008, 2008, 1.
4. Boyle, R.; Dolphin, D. Photochem. Photobiol. 1996, 64, 469.
3
.
Compound
Porphyrin
Cytotoxicity (IC50
,
l
M)
5.
6.
7.
8.
9.
Anantha, N. V.; Azam, M.; Sheardy, R. D. Biochemistry 1998, 37, 2709.
Mettath, S.; Munson, B. R.; Pandey, R. K. Bioconjugate Chem. 1999, 10, 94.
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Hudson, B. P.; Sou, J.; Berger, D. J.; McMillin, D. R. J. Am. Chem. Soc. 1992, 114,
UV
Visible
>20
>20
0.18
0.06
0.30
H
6
7
8
2
TPP
>20
>20
0.17
0.16
1.24
8997.
TMPyP
10. Mestre, B.; Jakobs, A.; Pratviel, G.; Meunier, B. Biochemistry 1996, 35, 9140.
1
1. Wilson, W. D.; Lynda, R.; Zhao, M.; Lucjan, S.; Boykin, D. Biochemistry 1993, 32,
2
Tetraphenylporphyrin(H TPP); tetra(4-N-methylpyridyl)porphyrin(TMPyP).
4098.
1
1
1
2. Ishikawa, Y.; Yamashita, A.; Uno, T. Chem. Pharm. Bull. 2001, 49, 287.
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4. Sehgal, I.; Sibrian-Vazquez, M.; Graca, M.; Vicente, H. J. Med. Chem. 2008, 51,
6014.
that of TMPyP is 0.30
presence of UV light showing porphyrin 8 has shown higher photo-
toxicity (IC50 = 0.16 M) than TMPyP (IC50 = 1.24 M). The cytotox-
icity could be arising through localization of porphyrin–quinoxaine
conjugate 8 either in the cell membrane or mitochondria.
In summary, we have synthesized novel porphyrin–quinoxaline
conjugates 6, 7 and 8 and characterized. Their interactions with
ctDNA showed two distinct binding modes suggesting intercala-
tion followed by self-stacking along the DNA surface. The photocy-
lM. Similar results were also displayed in
1
1
5. Kumar, D.; Mishra, B.; Chandrashekar, K. P.; Kumar, A.; Akamatsu, K.; Kusaka,
E.; Ito, T. Chem. Commun. 2013, 683.
6. Chaloin, L.; Bigey, P.; Loup, C.; Marin, M.; Galeotti, N.; Piechaczyk, M.; Heitz, F.;
Meunier, B. Bioconjugate Chem. 2001, 12, 691.
l
l
1
1
7. Bisland, S. K.; Singh, D.; Gariepy, J. Bioconjugate Chem. 1999, 10, 982.
8. Sibrian-Vazquez, M.; Jensen, T. J.; Hammer, R. P.; Vicente, M. G. H. J. Med. Chem.
2006, 49, 1364.
19. Gomer, C. J. Photochem. Photobiol. 1991, 54, 1093.
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2008, 11, 56.
totoxicity of conjugate 8 (IC50 = 0.06
showed fivefold more potency than the standard TMPyP
IC50 = 0.30 M), and thus leading to be a potential candidate in
lM) against A549 cancer cells
2
3. (a) Toshima, K.; Takano, R.; Ozawa, T.; Matsumura, S. Chem. Comm. 2002, 212;
(
l
(
6
b) Aggarwal, R.; Sumrana, G.; Kumar, V.; Mittal, A. Eur. J. Med. Chem. 2011, 46,
083.
developing a potent photocytotoxic agent for PDT. Further struc-
ture–activity relationship studies of these conjugates are in
progress.
24. Adler, A. D.; Longo, F. R.; Finarelli, J. D. J. Org. Chem. 1967, 32, 476.
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2
2
6. Harms, A. E. Org. Process Res. Dev. 2004, 8, 666.
7. Spectral data of cationic porphyrin–quinoxaline conjugate 8: 1H NMR (400 MHz,
Acknowledgments
DMSO-d
.72 (d, 2H J = 4 Hz), 8.48–8.44 (m, 7H), 8,42– 8.40 (m, 1H), 4.84 (s, 9H), ꢁ2.98
s, 2H). 13C NMR (100 MHz, DMSO-d
) d: 162.82, 151.66, 151.00, 148.08,
46.65, 145.37, 144.36, 144.13, 142.75, 138.68, 137.32, 133.16, 132.13, 131.89,
31.46, 131.01, 130.76, 130.37, 129.42, 127.76, 126.68, 120.65, 119.20, 116.97,
6
) d: 9.58–9.55 (m, 6H), 9.16–9.03 (m, 8H), 8.99–8.87 (m, 6H), 8.75–
8
(
6
We are grateful to the Department of Science & Technology and
University Grants Commission, New Delhi (under SAP) for the
financial support. We are thankful to RSIF, Chandigarh and AIRF,
JNU for the NMR and MALDI spectra. B.M. is thankful to CSIR,
New Delhi for SRF (F. No. 09/719(0042) /2011.EMR-I).
1
1
48.48. UV–vis kmax (nm): 422 (log
log = 3.6), 656 (log
e
= 5.1), 518 (log
e = 3.9), 582 (log
e
= 3.7), 601
ꢁ
1
(
e
e
= 3.3). IR (KBr) (
mmax cm ): 1138, 1402, 1483, 1514,
1
8
643, 1687, 3010. MALDI-TOF m/z: calcd for C53H N10O: 833.3448; Found:
33.3415 (M ). HPLC purity: 99.71%.
41
+
2
8. (a) Carvlin, M.; Fiel, R. J. Nucleic Acids Res. 1983, 11, 6121; (b) McMillin, D. R.;
McNett, K. M. Chem. Rev. 1998, 98, 1201; (c) Mohammadi, S.; Perree-Fauvet, M.;
Gresh, N.; Hillairet, K.; Taillandier, E. Biochemistry 1998, 37, 6165; (d)
Pasternack, R. F.; Gibbs, E. J.; Villafranca, J. J. Biochemistry 1983, 22, 2406.
Supplementary data
Supplementary data (experimental procedures and spectral
29. (a) Strickland, J. A.; Marzilli, L. G.; Wilson, W. D. Biopolymers 1990, 29, 1307; (b)
Strahan, G. D.; Lu, D.; Tsuboi, M.; Nakamoto, K. J. Phys. Chem. 1992, 96, 6450.
3
0. Pasternack, R. F.; Gibbs, E. J.; Gaudemer, A.; Antebi, A.; Bassner, S.; Poy, L. D.;
Turner, D. H.; Williams, A.; Laplace, F.; Lansard, M. H.; Merienne, C.; Perre-
Fauvet, M. J. Am. Chem. Soc. 1985, 107, 8179.
3
3
1. Mukundan, N. E.; Petho, G.; Dixon, D. W.; Marzilli, L. G. Inorg. Chem. 1995, 34,
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1