Synthesis and In vitro Anticancer Activity of Novel Quinazoline Derivatives Containing Thiosemicarbazone Structure

To find new EGFR inhibitors, 15 novel quinazoline derivatives containing thiosemicarbazone structure were designed and synthesized from 2-amino-4,5-dimethoxybenzoic acid and formamidine acetate by the cyclization, chlorination, amination and condensation reactions. All structures of target compounds were confirmed by H-1 NMR,C-13 NMR, HRMS and elemental analysis. The in vitro anticancer activities of compounds 6a-6o against EGFR over-expressing of MCF-7(Human breast cancer), A549(Human pulmonary adenocarcinoma) and PC3(Human prostate cancer) cell lines were tested using colorimetric MTT assay. The results indicated that several compounds showed potent activity. Compounds 6a and 6o were more potent than Lapatinib, but slightly weaker than ADM against the three cell lines. The IC50 values of compounds 6a and 6o against MCF-7 cell line were 6.97 and 6.99 mu mol/L, against A549 were 5.15 and 3.11 mu mol/L and against PC3 were 2.30 and 1.42 mu mol/L, respectively. Preliminary structure-activity relationship was also discussed.