Cytotoxic constituents from Brazilian red propolis and their structure-activity relationship

Several classes of flavonoids [flavanoids ( 1 - 10), flavonol ( 11), isoflavones ( 12 - 18), isoflavanones ( 19 - 22), isoflavans ( 23 26), chalcones ( 27 - 30), auronol ( 31), pterocarpans ( 32 - 37), 2-arylbenzofuran ( 38), and neoflavonoid ( 39)] and lignans ( 40 - 42) isolated from the MeOH extract of Brazilian red propolis were investigated for their cytotoxic activity against a panel of six different cancer cell lines including murine colon 26-L5 carcinoma, murine B16-BL6 melanoma, murine Lewis lung carcinoma, human lung A549 adenocarcinoma, human cervix HeLa adenocarcinoma, and human HT-1080. fibrosarcoma cell lines. Based on the observed results, structure - activity relationships were discussed. Among the tested compounds, 7-hydroxy-6-methoxy flavanone ( 3) exhibited the most potent activity against B16-BL6 (IC(50), 6.66 mu M), LLC ( IC(50), 9.29 mu M), A549 ( IC(50), 8.63 mu M), and HT- 1080 ( IC(50), 7.94 mu M) cancer cell lines, and mucronulatol ( 26) against LLC ( IC(50), 8.38 mu M) and A549 ( IC(50), 9.9 mu M) cancer cell lines. These activity data were comparable to those of the clinically used anticancer drugs, 5-fluorouracil and doxorubicin, against the tested cell lines, suggesting that 3 and 26 are the good candidates for future anticancer drug development. (C) 2008 Elsevier Ltd. All rights reserved.