The topoisomerase-based design and development for the shift from an antibacterial to an antitumor agent have been a new strategy in the fluoroquinolone field. To further expand the research of the C-3 fused heterocyclic rings attached to the quinolinone skeleton, the key intermediate of 1-amino-5-mercapto- 1,3,4-triazole (5) derived from the C-3 carboxyl group of enrofloxacin 1 was synthesized, then, the corresponding fused heterocyclic ring, s-triazolo[2,1-b][1,3,4]thiadiazin-3-one (7), was produced by a cyclocondensation of 5 with chloroacetic acid. The further modification for the above fused core 7 by a Perkin reaction with substituted benzaldehydes yielded the title compounds, 1-cyclopropyl-7-(4-ethylpiperazin-1-yl)-6- fluoro-3-{2-(substituted-benzylidene)-3,4-dihydro-[1,3,4]triazolo[2,1-b][1,3,4]thiadiazin-3-(2H)-one-5- yl)}quinolin-4-(1H)ones (8), respectively. The structures of new compounds synthesized were characterized by elemental analysis and spectral data, and their in vitro anticancer activity against the three cancer cell lines of CHO, HL60 and L1210 was evaluated. The bioactive assay showed that all new compounds, especially the intermediate 6 exhibited a significant antitumor activity with a range of the micromole concentrations for IC50 value. Thus, the C-3 mono or fused heterocycle-based substituted antitumor fluoroquinolones are valuable for further study.

Key words: fluoroquinolone, s-triazole, s-triazolothiadiazinone, anticancer evaluation