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ChemComm
The authors thank DST, New Delhi (SR/S1/OC 77/2006) for
nonviable cells having condensed nuclei and compromised
35
membranes were observed for the 11 treated samples. Further
studies are now ongoing to investigate the mechanisms of
phototoxicity, but it seems that 12 induces significant apoptosis in
A549 cells.
the financial support. BM is grateful to CSIR, New Delhi for
fellowship (F. No. 09/719(0042) /2011.EMR-I).
5
Notes and references
aDepartment of Chemistry, Birla Institute of Technology & Science,
Table 1 Phototoxicity results of the porphyrin conjugates 11 and 12
IC50 (µM)a
A549
40 Pilani- 333 031 India; E–mail: dalipk@bits–pilani.ac.in
bDepartment of Energy and Hydrocarbon Chemistry, Graduate School of
Engineering, Kyoto University, Kyoto, 615–8510, Japan;
E–mail: takeoit@scl.kyoto–u.ac.jp
Porphyrin
dark
Visible
UV–A
>100
>100
>100
24.7
0.07
1.24
43.1
0.06
0.30
11
12
TMPyP
a The results are the mean values of at least 3 independent experiments.
45 †Electronic Supplementary Information (ESI) available: [Experimental
section, DNA cleavage assay, Cell viability assay, Synthesis of β–
carboline azide and
DOI: 10.1039/b000000x/
porphyrin–β–carboline
conjugate].
See
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Based Drugs, 2008, 1.
10
Fig. 2 Photoinduced DNA cleavage by 12. ΦX174 supercoiled DNA (0.5
µg) was incubated with 12 (20 µM) in 20 µL of Tris–HCl (20 mM, pH
7.2) containing NaCl (20 mM), DMSO (2.5 vol%) at ambient temperature
55 2. (a) M. R. Hamblin and P. Mroz, in Advances in Photodynamic
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15 in the dark for 30 min, and then exposed to (lanes 1–5) UV–A or (lanes
6–10) visible light. Lanes 1 and 6, DNA + 12; lanes 2 and 7, DNA + 12 +
hν, 15 min; lanes 3 and 8, DNA + 12 + hν, 30 min; lanes 4 and 9, DNA +
12 + hν, 60 min; lanes 5 and 10, DNA alone.
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20
1
16. Spectral data: cationic porphyrin–β-carboline conjugate 12. H NMR
Fig. 3 Hoechst 33342 staining of (a–c) 11 (50 µM) or (d–f) 12 (0.1 µM)
treated A549 cells to identify nuclear morphology: (a, d) incubated in the
dark, (b, e) exposed to UV–A (4 mW, 10 min), and (c, f) exposed to
25 visible light (2 mW, 10 min).
(500 MHz, DMSO–d6) δ 9.49 – 9.42 (m, 8H), 9.18 – 8.99 (m, 15 H),
8.23 – 8.15 (m, 4H), 7.77 (s, 1H), 7.64 (d, J = 8.2 Hz, 2H), 7.16 – 7.14
(m, 1H), 5.88 (s, 2H), 5.27 (t, J = 7.2 Hz, 2H), 4.95 (t, J = 7.3 Hz,
2H), 4.73 (s, 9H), 4.60 (s, 3H), −2.90 (s, 2H); 13C NMR (126 MHz,
DMSO) δ 157.92, 157.08, 156.89, 148.68, 147.96, 145.84, 144.64,
144.64, 143.54, 139.94, 136.11, 134.46, 132.58, 131.42, 130.21,
126.21, 122.88, 116.92, 115.93, 115.78, 114.78, 114.21, 107.79,
71.56, 58.93, 48.37, 46.47, 31.22; MALDI–TOF: calcd for
C61H52N12O: 968.4365; found 968.4357 [M]+; HPLC purity: 99.28 %
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90
In summary, we have prepared a novel water soluble cationic
porphyrin–β–carboline conjugate employing click reaction which
exhibited high photocytotoxicity toward A549 cancer cells when
compared to a tumor–localizing and potent photosensitizing
30 agent, TMPyP. This work demonstrates that porphyrin–β–
carboline conjugate 12 is a potential candidate for PDT. Further
mechanistic and structure-activity relationship studies of
porphyrin–β–carboline conjugates are underway in our laboratory
and will be reported in near future.
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