tailieunhanh - Anticancer agents - Part 48: Alpha-substituted 2’,5’-dihydroxychalcones: synthesis and cytotoxicity

A series of alpha-substituted 2’,5’-dihydroxychalcones bearing a cyanide, bromine, or methyl group at alpha-position were synthesized and evaluated for in vitro cytotoxicity against three cancer cell lines, including B16, murine melanoma, HCT116 (colon cancer), A431 (human epidermoid carcinoma), and HUVEC (human umbilical venous endothelial cell). The synthesized chalcones showed significant cytotoxicity against most of cell lines, with IC50 values ranging from to 10 µg/mL. | Journal of Chemistry Vol. 44 2 P. 239 - 244 2006 ANTICANCER AGENTS. PART 48. ALPHA-SUBSTITUTED 2 5 -DIHyDROXyCHALCONES SyNTHESIS AND CyTOTOXICITy Received 28 February 2005 NGUyEN HAI NAM1 AND NGUyEN MANH CUQNG2 1Department of Pharmaceutical Chemistry Hanoi University of Pharmacy 2Institute of Chemistry Vietnamese Academy of Science and Technology SUMMARy A series of alpha-substituted 2 5 -dihydroxychalcones bearing a cyanide bromine or methyl group at alpha-position were synthesized and evaluated for in vitro cytotoxicity against three cancer cell lines including B16 murine melanoma HCT116 colon cancer A431 human epidermoid carcinoma and HUVEC human umbilical venous endothelial cell . The synthesized chalcones showed significant cytotoxicity against most of cell lines with IC50 values ranging from to 10 ụg mL. I - INTRODUCTION In our research program to develop anticancer and antiangiogenic agents from medicinal plants we have isolated a simple phenol methyl 3 4-dimethoxycaffeate 1 figure 1 1 . This compound shows very potent cytotoxicity against several murine and human cancer cell lines 1 . Intrigued by its activity we have synthesized a series of 3-aryl-2-propenoates 2 and rigid 2 5-dihydroxycinnamates 3 4 . From these studies we found methyl 2 5-dihydroxycinnamate 2 figure 1 as a very potent cytotoxic agent with IC50 values in NCI US National Cancer Institute 60 cancer cell panel at low microgram range. In continuity we prepared two series of 2 5-dihydroxychalcones not shown and 2 5 -dihydroxychalcones 3 figure 1 5 - 7 . Most of the synthesized chalcones exhibited significant cytotoxicity against both murine and human cancer cells with IC50 values in low microgram mL range. Three most potent compounds were 3a 3b and 3c. These three chalcones also exhibited considerable in vivo antitumor activity with tumor mass inhibition rates recorded at 47 - 61 when tested in BDF1 mice bearing B16 murine melanoma cells 7 8 . The results further spurred our interest in .