Prenylated flavonoids from Glycyrrhiza uralensis as promising anti-cancer agents: a preliminary structure-activity study

Prenylated flavonoids are mainly distributed in Leguminosae and Moraceae plants, and they have been reported to possess various biological activities. Previously, we have reported a prenylated isoflavonoid, isoangustone A（IAA） from licorice（Glycyrrhiza uralensis）, which induces apoptosis in colorectal cancer cells by disrupting mitochondrial functions. In the present study, we compared a group of flavonoids from licorice with IAA for their anti-proliferation activities and effects on intracellular signaling. The results indicated that the isoprenyl groups on the A and B rings, the hydroxyl groups at the ortho position of isoprenyl on A ring and the conjugated plane of C ring might contribute to the anti-cancer activity of prenylated flavonoids. Based on the above structure-activity relationship, we further identified four prenylated flavonoids with similar anti-cancer activities from licorice. Taken together, our present study established a preliminary structure-activity relationship of anti-cancer prenylated flavonoids, and our data provided important leading compounds from licorice, which deserved further research and development.

IC5, a dithiocarbamate derivative, inhibits colon cancer cell proliferation in vitro and colitis-associated colorectal carcinogenesis in vivo

Colorectal cancer （CRC） is one of the leading causes of cancer-related deaths, and inflammatory bowel diseases and dysregulated cell proliferation play important roles in colorectal carcinogenesis. Therefore, inhibition of inflammatory signaling and cell proliferation is used as a major strategy for chemoprevention of CRC. In the present study, it was found that IC5, a dithiocarbamate derivative, could inhibit the proliferation of LoVo human colon cancer cells in a concentration-dependent manner, with an IC50 of 22 gM. The anti-proliferation effect of IC5 was accompanied by a significant cell cycle arrest in G2/M phase. Further study revealed that IC5 significantly inhibited NF-~B signaling in LoVo cells, suggesting that IC5 could inhibit inflammatory responses. We then evaluated the in vivo efficacy of IC5 to inhibit colitis-associated colorectal carcinogenesis using an azoxymethane （AOM）/dextran sodium sulfate （DSS） mouse model. AOM/DSS treatment resulted in a CRC incidence of 58.3%, while the incidences were decreased to 37.5% and 25% in mice orally administered with 50 and 100 mg/kg IC5, respectively. In addition, IC5 also reduced the plasma levels of alanine aminotransferase and asparatate aminotransferase. Taken together, these results suggested that IC5 could prevent colitis-associated colorectal carcinogenesis, and more attention should be paid to it as a cancer chemopreventive agent in further investigation.

Synthesis and cytotoxicity of kaempferol derivatives

Abstract： In the present study, we developed a simple approach for the structural modifications ofkaempferol （1）. A new compound, 3,5-dihydroxy-2-（4-hydroxyphenyl）-6,8,8-tris（3-methylbut-2-en-1-yl）-4H-chromene-4,7（SH）-dione （5） together with three known compounds, 8-prenylkaempferol （Z）, 6-prenylkaempferol （3） and 6,8-diprenylkaempferol （4）, were synthesized under different reaction conditions. All of derivatives were synthesized in a structural modification way for the first time. Their structures were primarily elucidated by NMR and MS analyses. Compounds 2, 3 and 5 exhibited prominent cytotoxic activity against MDA-231 （IC50 values were 9.45±0.20 μM, 7.15±0.37 μM and 6.92±0.30 μM, respectively） and MCF-7 （ICso values were 10.08±0.57 0M, 10.04±0.23 μM and 2.15±0.20 μM, respectively） breast cancer cells.