914
V. Srivastava et al. / Bioorg. Med. Chem. Lett. 16 (2006) 911–914
4. Tatum, J. H.; Baker, R. A.; Berry, R. E. Phytochemistry
1987, 26, 2499.
5. Hagiwara, H.; Sato, K.; Suzuki, T.; Ando, M. Heterocy-
cles 1999, 51, 497.
128.57, 128.43, 127.85, 125.95, 125.95, 124.52, 124.33,
123.40, 120.80, 112.80. EI-Mass (GC–MS, MeOH);244
[M]+, Product ions; 215, 106. Elemental analysis calcd for
C18H12O: C, 88.52; H, 4.92. Found: C, 88.76; H, 4.74.
´
6. Kamboj, V. P.; Chandra, H.; Setty, B. S.; Kar, A. B.
Contraception 1970, 1, 29.
7. Weill-Thevenet, N.; Buisson, J.-P.; Royer, R.; Hofnung,
M. Mutat. Res. Lett. 1982, 104, 1.
13. Woerdenbag, H. J.; Moskal, T. A.; Pras, N.; Malingre, T.
M.; Farouk, S.; El-Feraly, H.; Kampinga, H.; Konings, A.
W. T. J. Nat. Prod. 1993, 56, 849.
14. General experimental procedure for the synthesis of aryl
naphtho[2,1b] furans: Synthesis of 1-(30,40,50-trimethoxy)
phenyl naphtho[2,1b]furan (8). In a 25 ml round-bot-
tomed flask 30,40,50-trimethoxy benzoyl naphthalene 2-O-
acetic acid (5, 100 mg, 0.25 mmol) was taken in dry
dichloromethane (10 ml). To this 1-hydroxy benzotriaz-
ole (80 mg, 0.63 mmol), EDC-HCl (120 mg, 0.63 mmol)
and triethyl amine (0.5 ml) were added. The reaction
mixture was stirred at room temperature for 20 min.
Now to this mixture 3,4,5-trimethoxy aniline (60 mg,
0.32 mmol) was added and the reaction mixture was
refluxed for 2 h. After completion of the reaction, 20 ml
water was added to this and stirred for 10 min. It was
extracted with dichloromethane (30 ml · 3) and washed
with water. The organic layer was dried over anhydrous
sodium sulfate and distilled off to get a residue. The
residue was passed through a small column of silica gel
(60–120 mesh) and eluted with hexane–ethyl acetate. The
compound 8 was obtained in 8–10% ethyl acetate–
hexane as an oil (89%).
15. In vitro anticancer activity of phenyl naphtho[2,1b]furans
using MTT assay. Cytotoxicity testing in vitro was done
by the method of Woerdenbag et al.13 2 · 103 cells/well
were incubated in the 5% CO2 incubator for 24 h to enable
them to adhere properly to the 96-well polystyrene
microplate (Grenier, Germany). Test compound dissolved
in 100% DMSO (Merck, Germany) in at least five doses
was added and left for 6 h after which the compound plus
media was replaced with fresh media and the cells were
incubated for another 48 h in the CO2 incubator at 37 ꢁC.
The concentration of DMSO used in our experiments
never exceeded 1.25%, which was found to be non-toxic to
cells. Then, 10 ll MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-
diphenyltetrazolium bromide; Sigma M 2128] was added,
and plates were incubated at 37 ꢁC for 4 h. One hundred
microlitres of dimethyl sulfoxide (DMSO, Merck, Germa-
ny) was added to all wells and mixed thoroughly to
dissolve the dark blue crystals. After a few minutes at
room temperature to ensure that all crystals were dis-
solved, the plates were read on a SpectraMax 190
Microplate Elisa reader (Molecular Devices Inc. USA) at
570 nm. Plates were normally read within 1 h of adding
the DMSO. The experiment was done in triplicate and the
inhibitory concentration (IC) values were calculated as
follows:
8. Ribeiro-Rodrigues, R.; dos Santos, W. G.; Oliveira, A. B.;
Snieckus, V.; Romanha, A. J. Bioorg. Med. Chem. Lett.
1995, 5, 1509.
9. Mehrotra, P. K.; Karkun, J. N.; Kar, A. B. Contraception
1973, 7, 115.
10. For review please see: (a) Hou, X. L.; Cheung, H. Y.; Hon,
T. Y.; Kwan, P. L.; Lo, T. H.; Tong, S. Y.; Wong, H. N.
C. Tetrahedron 1998, 54, 1955; (b) Ghera, E.; Maurya, R.
Tetrahedron Lett. 1987, 28, 709; (c) Naruta, Y.; Uno, H.;
Maruyama, K. Tetrahedron Lett. 1981, 22, 5221; (d)
Sestelo, J. P.; Real, M. D.; Mourino, A.; Sarandeses, L. A.
Tetrahedron Lett. 1999, 40, 985; (e) Park, K. K.; Jeong, J.
Tetrahedron 2005, 61, 545.
11. Negi, A. S.; Darokar, M. P.; Chattopadhyay, S. K.; Garg,
A.; Bhattacharya, A. K.; Srivastava, V.; Khanuja, S. P. S.
Bioorg. Med. Chem. Lett. 2005, 15, 1243.
12. Selected physical data.
Compound 8: yield = 89%; mp = oil, IR = 1582, 1462,
1
1218, 1127, 770, 670. H NMR (CDCl3, 300 MHz) d 3.79
(s, 6H, 30 and 50 OCH3), 3.89 (s, 3H, 40-OCH3), 6.72 (s,
2H, 20 and 60 CH of phenyl ring), 7.34–7.36 (distorted t,
2H, J = 8.19 Hz), 7.57–7.59 (d, 1H, J = 5.79 Hz), 7.625 (s,
1H, CH of furan ring), 7.67–7.70 (d, 1H, J = 9.0 Hz),
7.85–7.87(d, 1H, J = 7.41 Hz), 7.9–8.02 (d, 1H,
J = 7.98 Hz); 13C NMR (CDCl3, 75.47 MHz) d 153.83,
153.83, 153.55, 141.59, 131.30, 129.32, 129.06, 128.82,
126.39, 125.33, 124.87, 124.79, 123.88, 121.11, 120.62,
113.41, 109.72, 107.81, 61.37, 56.70, 56.70. Electrospray
Mass (CH3CN); m/z 335.5 [M+H]+ (86.67%), 357.2
[M+Na]+ (66%), 373.1 [M+K]+ (48.8%), Product ions;
320.1 [Mꢀ14]+, 276, 141.1. Elemental analysis calcd for
C21H18O4: C, 75.45; H, 5.39. Found: C, 75.86; H, 5.68.
1
Compound 9: yield = 91 %; mp = oil, H NMR (CDCl3,
300 MHz) d 3.83 (s, 3H, OCH3), 6.96 (d, 2H, 20 and 60 CH,
J = 8.68 Hz), 7.25–7.37 (m, 2H), 7.42–7.45 (d, 2H, 30 and
50 CH, J = 8.65 Hz), 7.58 (d, 1H, J = 5.16 Hz), 7.622 (s,
1H, CH of furan ring), 7.67 (d, 1H, J = 8.97 Hz), 7.86 (d,
1H, J = 7.74 Hz), 7.92 (d, 1H, J = 8.19 Hz); 13C NMR
(CDCl3, 75.47 MHz) d 159.94, 153.54, 141.94, 131.39,
131.39, 131.26, 129.25, 128.88, 126.29, 126.19, 125.68,
124.66, 124.45, 123.74, 121.42, 114.52, 114.52, 112.99,
55.74. EI-Mass (GC–MS, MeOH); 274 [M]+, Product
ions; 259, 202. Elemental analysis calcd for C19H14O2: C,
83.21; H, 5.11. Found: C, 83.44; H, 4.96
1
Compound 10: yield = 73%; mp = oil, H NMR (CDCl3,
%inhibition ¼ ½1 ꢀ ODð570 nmÞ of sample well=OD
ð570 nmÞ of control wellꢁ ꢂ 100.
300 MHz) d 7.23–7.25 (d, 1H, J = 7.7 Hz), 7.28–7.31
(d,1H, J = 8.25 Hz), 7.33 (d, 2H, J = 7.68 Hz), 7.37–7.38
(m, 1H), 7.44–7.47 (dd, 2H, J = 9.22 and 1.6 Hz), 7.52–
7.59 (t, 2H, J = 10.1 Hz), 7.62 (s, 1H, CH of furan ring),
7.76–7.79 (d, 1H, J = 7.9 Hz), 7.86–7.89 (d, 1H,
J = 8.2 Hz); 13C NMR (CDCl3, 75.47 MHz) d 153.24,
141.67, 133.20, 130.92, 129.89, 129.19, 128.91, 128.57,
IC90 is the concentration lg/mL required for 90% inhibi-
tion of cell growth as compared to that of untreated
control.