Synthesis and Structure-Activity Relationship Study of 1-Phenyl-1-(quinazolin-4-yl)ethanols as Anticancer Agents

ACS Med Chem Lett. 2015 Jan 10;6(3):287-91. doi: 10.1021/ml5004684. eCollection 2015 Mar 12.


A quinazoline derivative PVHD121 (1a) was shown to have strong antiproliferative activity against various tumor-derived cell lines, including A549 (lung), NCI-H460 (lung), HCT116 (colon), MCF7 (breast), PC3 (prostate), and HeLa (cervical) cells with IC50 values from 0.1 to 0.3 μM. A structure-activity relationship (SAR) study at the 2- and 4-position of the quinazoline core lead to the discovery of more potent anticancer agents (14, 16, 17, 19, 24, and 31). The results of an in vitro tubulin polymerization assay and fluorescent-based colchicine site competition assay with purified tubulin indicated that 1a inhibits tubulin polymerization by binding to the colchicine site.

Keywords: Quinazoline; anticancer; colchicine binding site; structure−activity relationship study; tubulin inhibitor.