Synthesis of 2-styrylchromones as a novel class of antiproliferative agents targeting carcinoma cells

A series of 2-styrylchromone analogs were synthesized and examined for their antiproliferative effects on a panel of carcinoma cells. Among the tested agents, only 4m exhibited a moderate activity with an IC(50) value of 28.9 mu M against PC-3 cells which indicates the selectivity of PC-3 cells in response to 2-styrylchromones. In addition, 4q demonstrated the most antiproliferative effect with an IC50 value of 4.9 mu M against HeLa cells. Flow cytometric analysis and DAPI staining revealed that HeLa cells exposed to 4q as low as 5 mu M induced cell death through sub-G1 arrest and DNA fragmentation. Furthermore, CoMFA analysis of tested 2-styrylchromones resulted in a q(2) of 0.459 to generate a 3D-QSAR model on BT483 cell line. Together, these results suggest a potential structural optimization and pharmacological study of 2-styrylchromones. (C) 2009 Elsevier Masson SAS. All rights reserved.