Synthesis and antiproliferative activity of 3- and 7-styrylcoumarins

Abstract

A series of styrylcoumarins were obtained via Mizoroki-Heck reactions between 3-bromo-4-methyl-7-(octyloxy)-2H-chromen-2-one or 2-oxo-2H-chromen-7-yl trifluoromethanesulfonate and functionalized styrenes. The structures of the products were elucidated by spectroscopic analysis. All compounds were evaluated against SW480 and CHO-K1 cell lines. A number of hybrids showed good antiproliferative activity. Among the tested compounds, hybrids 6e, 10c and 10d, exhibited the highest activity (IC50-SW480/48h = 6,92; 1,01 and 5,33 µM, respectively) and selectivity (IS48h = >400; 67,8 and 7,2, respectively). In addition, these compounds were able to preserve their activities over time. The results achieved by these hybrids were even better than the lead compounds (coumarin and resveratrol) and the standard drug (5-FU). As regards structure-activity relationship it seems that the location of the styryl group on the coumarin structure and the presence of the hydroxyl group on the phenyl ring were determinant for the activity.

Investigation of the cytotoxicity of bioinspired coumarin analogues towards human breast cancer cells

“…m.p. 48–50 °C) [ 24 ]. 1 H ΝMR(600 MHz, DMSO): δ (ppm) 8.58 (d, J = 8.4 Hz, 1H, H-5), 6.78 (dd, J = 9 Hz & J = 2.4 Hz, 1H, H-6), 6.68 (d, J = 2.4 Hz, 1H, H-8), 6.15 (s, 1H, H-3), 4.06 (t, J = 6.6 Hz, 2H, H-1′), 2.39 (s, 3H, 4-CH 3 ), 1.72 (m, 2H, H-2′), 1.40 (m, 2H, H-7′), 1.29 (m, 8H, H-3′ & H-5′ & H-4′ & H-6′), 0.86 (t, J = 6.9 Hz, 3H, 7′-CH 3 ).…”

“…Coumarin derivatives have gained high scientific interest as promising drug candidates since they possess multiple pharmacological properties [10][11][12][13], such as antioxidant [14][15][16], antibacterial [17,18], antimicrobial [18], antiviral [13], hepatoprotective [19] and anti-inflammatory effects [20][21][22]. Natural and synthetic coumarins have been also reported as effective chemopreventive and anticancer agents in vitro [23][24][25][26] and in vivo [27].…”

An Overview of Coumarin as a Versatile and Readily Accessible Scaffold with Broad-Ranging Biological Activities

“…The cytotoxicity of 20 was explained also by docking studies which highlighted that it forms important H-bonds with Arg364, Asp533, Gln633 and 5′-thio-2′ deoxyguanosine phosphonic acid of the DNA backbone. Herrera et al synthesized a series of 3-and 7-styrylcoumarins, some of which showed antiproliferative activity on SW480 human colon adenocarcinoma cells [48]. Among them, 7-(4-hydroxy-3,5-dimethoxystyryl)-2H-chromen-2-one (21, Figure 10) showed the highest activity (IC50 = 1.01 μM) as it was capable of inducing apoptosis in SW480 cells, probably by modulating the tumor-suppressor protein p53.…”

“…These evidences guided Diao and collaborators in the choice of diethylene glycol as a linker [47]. Ten compounds were tested on HepG2 (liver carcinoma), HeLa (cervical cancer), A549 (lung adenocarcinoma), DU145 (prostatic cancer), SKOV3 (ovarian carcinoma), MCF-7 (breast cancer) and drug-resistant MCF-7/DOX (doxorubicin-resistant MCF-7) Herrera et al synthesized a series of 3-and 7-styrylcoumarins, some of which showed anti-proliferative activity on SW480 human colon adenocarcinoma cells [48]. Among them, 7-(4-hydroxy-3,5-dimethoxystyryl)-2H-chromen-2-one (21, Figure 10) showed the highest activity (IC 50 = 1.01 µM) as it was capable of inducing apoptosis in SW480 cells, probably by modulating the tumor-suppressor protein p53.…”

“…Herrera et al synthesized a series of 3- and 7-styrylcoumarins, some of which showed anti-proliferative activity on SW480 human colon adenocarcinoma cells [ 48 ]. Among them, 7-(4-hydroxy-3,5-dimethoxystyryl)-2 H -chromen-2-one ( 21 , Figure 10 ) showed the highest activity (IC 50 = 1.01 μM) as it was capable of inducing apoptosis in SW480 cells, probably by modulating the tumor-suppressor protein p53.…”