Concise Article
MedChemComm
vacuum. When necessary, the product was crystallized from
diethyl ether or pentane.
because a higher cytotoxicity against T24 cells, which repre-
sent a higher degree of malignancy compared to RT4, was
obtained. In addition, 3c increased the cell number in the
sub-G1 phase inducing apoptosis, which was confirmed by
annexin V staining of this cell line after 24 h of treatment.
Therefore, the cytotoxic activity determined for 7,8-dihydroxy-
4-methyl-2-oxo-2H-chromene-5-carboxylic acid, 3c, suggests
the need for further testing in vivo in a bladder cancer animal
model.
7-Hydroxy-4-methyl-2H-chromen-2-one (3a)38. m.p. = 187–
1
189 °C; H NMR (300 MHz, CDCl3) δ (ppm) 2.37 (s, 3H, CH3),
6.04 (s, 1H, CH), 6.76–6.84 (m, 2H, CHarom), 7.43 (d, J = 8.6
Hz, 1H, CHarom), 10.13 (br s, 1H, OH); 13C NMR (75 MHz,
CDCl3) δ 17.9, 102.1, 109.9, 111.7, 112.5, 125.1, 152.6, 154.3,
160.5, 160.9.
7,8-Dihydroxy-4-methyl-2H-chromen-2-one (3b)39. m.p.
>250 °C; 1H NMR (300 MHz, CDCl3) δ (ppm) 2.38 (s, 3H,
CH3), 6.06 (s, 1H, CH), 6.85 (d, J = 8.6 Hz, 1H, CHarom), 7.02
(d, J = 8.6 Hz, 1H, CHarom); 13C NMR (75 MHz, CDCl3) δ 17.9,
108.8, 111.6, 112.7, 116.8, 133.7, 141.5, 148.2, 153.9, 161.7.
7,8-Dihydroxy-4-methyl-2-oxo-2H-chromene-5-carboxylic
acid (3c)40. m.p. >250 °C; 1H NMR (300 MHz, DMSO-d6) δ
(ppm) 2.43 (s, 3H, CH3), 6.87 (s, 1H, CH), 9.11 (s, 1H,
CHarom); 13C NMR (75 MHz, DMSO-d6) δ 20.2, 109.3, 111.3,
119.2, 120.9, 138.7, 146.7, 147.4, 148.2, 158.3, 168.0.
Acknowledgements
This work was supported by CNPq & Capes - Brazil. G. von
Poser, A. M. Battastini and V. L. Eifler-Lima are recipients of
Productivity Research Fellowships from CNPq. D. R. Vianna
acknowledges support from PNPD (project number 22
2683091).
7-IJAllyloxy)-4-methyl-2H-chromen-2-one (4)41. m.p. = 72–75
°C; 1H NMR (300 MHz, CDCl3) δ (ppm) 2.40 (s, 3H, CH3),
4.61 (d, J = 3.8 Hz, 2H, CH2), 5.33–5.36 (dd, Jcis = 10.4 Hz,
Notes and references
1 A. Jemal, F. Bray, M. M. Center, J. Ferlay, E. Ward and D.
Forman, Ca-Cancer J. Clin., 2011, 61, 90.
Jgem = 1.3 Hz, 1H, CH2), 5.42–5.48 (dd, Jtrans = 17.1 Hz, Jgem
=
1.4 Hz, 1H, CH2), 5.99–6.12 (m, 1H, CH), 6.14 (s, 1H, CH),
6.83 (d, J = 2.4 Hz, 1H, CHarom), 6.87–6.91 (dd, J1 = 8.8 Hz, J2
= 2.4 Hz, 1H, CHarom), 7.50 (d, J = 8.8 Hz, 1H, CHarom); 13C
NMR (75 MHz, CDCl3) δ 18.6, 69.2, 101.7, 111.9, 112.7, 113.6,
118.4, 125.5, 132.1, 152.5, 155.1, 161.3, 161.5.
2 A. Jemal, R. Siegel, E. Ward, Y. Hao, J. Xu and M. J. Thun,
Ca-Cancer J. Clin., 2009, 59, 249.
3 A. A. Memon, J. W. Chang, B. R. Oh and Y. J. Yoo, Cancer
Detect. Prev., 2005, 29, 255.
4 T. Nguyen-Khuong, M. Y. White, T. T. Hung, S. Seeto, M. L.
Thomas, A. M. Fitzgerald, C. E. Martucci, S. Luk, S. F. Pang,
P. J. Russell and B. J. Walsh, Proteomics, 2009, 9, 1892.
5 D. L. Lamm, D. E. Thor, S. C. Harris, J. A. Reyna, V. D.
Stogdill and H. M. Radwin, J. Urol., 1980, 124, 40.
6 H. W. Herr, D. D. Wartinger, W. R. Fair and H. F. Oettgen,
J. Urol., 1992, 147, 1023.
7 J. Stella, L. Bavaresco, E. Braganhol, L. Rockenbach, P. F.
Farias, M. R. Wink, A. A. Azambuja, C. H. Barrios, F. B.
Morrone and A. M. O. Battastini, Urol. Oncol.: Semin. Orig.
Invest., 2009, 28, 267.
8 A. Ozawa, N. Tanji, T. Kikugawa, T. Sasaki, Y. Yanagihara, N.
Miura and M. Yokoyama, BJU Int., 2010, 105, 1186.
9 L. Wu, X. Wang, W. Xu, F. Farzaneh and R. Xu, Curr. Med.
Chem., 2009, 16, 4260.
10 F. H. Dexeus, C. J. Logothetis, A. Sella, K. Fitz, R. Amato,
J. M. Reuben and N. J. Dozier, J. Clin. Oncol., 1990, 8, 329.
11 C. J. Wang, Y. J. Hsieh, C. Y. Chu, Y. L. Lin and T. H. Tseng,
Cancer Lett., 2002, 183, 168.
Ethyl
2-IJ4-methyl-2-oxo-2H-chromen-7-yloxy)acetate
(5)42,43. m.p. = 98–101 °C; H NMR (300 MHz, CDCl3) δ (ppm)
1.73 (t, J = 7.0 Hz, 3H, CH3), 2.67 (s, 3H, CH3), 4.32 (q, J = 7.1
Hz, 2H, CH2), 5.38 (s, 2H, CH2), 6.51 (s, 1H, CH), 7.18–7.79
(m, 3H, CHarom); 13C NMR (400 MHz, DMSO-d6) δ 14.5, 18.6,
61.3, 65.4, 101.9, 111.9, 112.8, 114.1, 126.9, 153.7, 154.9,
160.5, 161.0, 168.6.
1
4-Methyl-2-oxo-2H-chromen-7-yl-4-methylbenzenesulfonate
1
(6)43. m.p. >250 °C; H NMR (300 MHz, CDCl3) δ (ppm) 2.33
(s, 3H, Ar–CH3), 2.38 (s, 3H, CH3), 6.18 (s, 1H, CH), 6.76 (s,
1H, CHarom), 6.99 (d, J = 8.7 Hz, 1H, CHarom), 7.26 (d, J = 8.2
Hz, 2H, CHarom), 7.48 (d, J = 8.8 Hz, 1H, CHarom), 7.64 (d, J =
8.2 Hz, 2H, CHarom); 13C NMR (75 MHz, CDCl3) δ 18.7, 21.7,
110.8, 115.0, 118.7, 118.8, 125.7, 128.4, 130.0, 131.8, 146.0,
151.5, 151.7, 153.8, 160.0.
7-IJBenzyloxy)-4-methyl-2H-chromen-2-one (7). m.p. = 132–
134 °C; 1H NMR (300 MHz, DMSO-d6) δ (ppm) 2.37 (s, 3H,
CH3), 5.21 (s, 2H, CH2), 6.20 (s, 1H, CH), 7.00–7.06 (m, 2H,
CHarom), 7.34–7.49 (m, 5H, CHarom), 7.67 (d, 1H, CHarom); 13C
NMR (400 MHz, DMSO-d6) δ 18.5, 70.3, 102.0, 111.7, 113.1,
113.7, 126.9, 128.3, 128.5, 128.9, 136.7, 153.8, 155.1, 160.53,
161.74.
12 D. Yang, T. Gu, T. Wang, Q. Tang and C. Ma, Biosci.,
Biotechnol., Biochem., 2010, 74, 1430.
13 D. E. Zembower, S. Liao, M. T. Flavin, Z. Q. Xu, T. L. Stup,
R. W. Buckheit, A. Khilevich, A. A. Mar and A. K. J.
Sheinkman, J. Med. Chem., 1997, 40, 1017.
14 G. B. Bubols, D. R. Vianna, A. Medina-Remón, G. von Poser,
M. Lamuela-Raventos, V. Eifler-Lima and S. C. Garcia, Mini-
Rev. Med. Chem., 2013, 13, 334.
15 F. Chimenti, B. Bizzarri, A. Bolasco, D. Secci, P. Chimenti, A.
Granese, S. Carradori, D. Rivanera, A. Zicari, M. M. Scaltrito
and F. Sisto, Bioorg. Med. Chem. Lett., 2010, 20, 4926.
Conclusions
In summary, among all of the synthesized coumarins, 3c
exhibited the best cytotoxic potential against bladder cancer
cell lines, leading to a reduction in the viability of T24 cells.
These results may indicate selectivity for malignant cells
Med. Chem. Commun.
This journal is © The Royal Society of Chemistry 2015