Abstract: To further study an efficient modified route for transforming an antibacterial fluoroquinolone to an antitumor compound, an oxadiazole heterocyclic ring, 1,3,4-oxadiazole-thione, was used as an isostere of C-3 carboxylic group for pefloxacin 1, and a key intermediate, 1-ethyl-6-fluoro-7-(4-methyl-piperazin-1-yl)-3-(3H-1,3,4-oxadiazole-2-thione-5-yl)-quinolin-4(1H)-one 4(5), was designed and synthesized. The intermediate was then subjected to an aminomethylation reaction with secondary amines or substituted anilines and formaldehyde to afford the corresponding oxadiazole thione Mannch bases 6a~6j as the title compounds, respectively. The structures for ten title compounds were characterized by elemental analysis, 1H NMR and MS, and their anticancer activities in vitro against Hep-3B cancer cell lines were also evaluated. The results reveal that all the title compounds show more significant potent than that of parent compound 1, and those derived from aliphatic amines display higher activity than the aromatic amine compounds.

Key words: fluoroquinolone, isostere, oxadiazole thione, Mannich base, antitumor evaluation