Abstract: A combination of the structural features of dihydromyricetin and quinolone antineoplastic compounds gave rise to 3-hydroxy-4-quinolone motif. Starting from 3, 5-dimethoxyaniline, the target compounds were prepared through a reaction cascade, including reductive amination, Friedel-Crafts reaction, microwave assisted ring closure, BBr₃ catalyzed demethylation and Mannich reaction. Sixteen novel compounds were synthesized, and their structures were confirmed by IR, MS and ¹H NMR. The antiproliferative activities of the compounds against A549 and NCI-H 460 cells were tested in MTT assay. Several compounds exhibited moderate antiproliferative activities against both cell lines, of which, compound 11b displayed the most robust inhibition towards NCI-H 460. Preliminary structural-activity relationships indicated that introduction of isopentenyl into the N-1 position of 3-hydroxy-4-quinolone motif would significantly improve the potency of the compounds.