title: Synthesis and Structure-Activity Relationship Study of 1-Phenyl-1-(quinazolin-4-yl)ethanols as Anticancer Agents.
abstract: 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.
authors: Department of Material and Life Sciences, Faculty of Science and Technology, Sophia University , 7-1 Kioicho, Chiyoda-ku, Tokyo 102-8554, Japan.
authors: Kenta
authors: K
authors: Kuroiwa
authors: Graduate School of Pharmaceutical Sciences, University of Shizuoka , 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
authors: Hirosuke
authors: H
authors: Ishii
authors: Graduate School of Pharmaceutical Sciences, University of Shizuoka , 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
authors: Kenji
authors: K
authors: Matsuno
authors: Graduate School of Pharmaceutical Sciences, University of Shizuoka , 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
authors: Akira
authors: A
authors: Asai
authors: Department of Material and Life Sciences, Faculty of Science and Technology, Sophia University , 7-1 Kioicho, Chiyoda-ku, Tokyo 102-8554, Japan.
authors: Yumiko
authors: Y
authors: Suzuki
keywords: Quinazoline; anticancer; colchicine binding site; structure−activity relationship study; tubulin inhibitor