Abstract:

To discover efficient structural modification strategy for the conversion of antibacterial activity of fluoroquinolones into antitumor activity, an azole heterocycle modified with sulfide-ketone thiosemicarbazone chain was designed as the bioisosteric replacement of the C-3 carboxylic acid group. Consequently, novel s-triazole-based thiosemicarbazone derivatives(6a~6g) were synthesized from ofloxacin 1, respectively. The structures of the title compounds(6a~6g) were characterized by elemental analysis and spectral data, and the in vitro antitumor activity was also evaluated by the MTT assay. Compounds(6a~6g) exhibit more significantly antiproliferative activity than both of parent ofloxacin 1 and the corresponding sulfide-ketone intermediates(5a~5g). These thiosemicarbazones, particularly those containing nitro group or fluorine atom, have comparable activity to doxorubicin. Therefore, it suggests that an azole ring modified with functional side-chain as the bioisosteric replacement of the C-3 carboxylic group is favorable for an improvement of antitumor activity of fluoroquinolones.

Key words: fluoroquinolone, bioisosterism, s-triazole, sulfide, thiosemicarbazone, antitumor activity