Abstract: To discover an efficient route for the conversion of antibacterial fluoroquinolone to antitumor activity, s-triazole ring as an isostere modified by an oxadiazole ring corresponding to the C-3 carboxylic acid group for pefloxacin resulted in ten new title compounds, 1-ethyl- 6-fluoro-(4-methylypiperazin-1-yl)-3-［5-(5-aryl-［1, 3, 4］oxadiazol-2-methylsulfanyl)-4H-［1, 2, 4］-triazol-3-yl］-quinolin(1H)-4-ones( 7a - 7j ). Their structures were characterized by corresponding spectral data. The in vitro antitumor activity of the title compounds against L1210, HL60 and CHO cell lines exhibited significantly higher potency than parent pefloxacin. Thus, it suggests that it is necessary to retain a heterocycle instead of a C-3 carboxyl for antitumor fluoroquinolone compounds.