ABSTRACT
OBJECTIVE: To discover an efficient strategy for a conversion of the antibacterial activity into an antitumor activity. METHODS: Pharmacophore and scaffold hopping-based rational drug design principles, the title fluoroquinolone C-3 thiazolotriazole unsaturated ketones (6a-6l) were designed and synthesized with a S-triazole ring and α,β-unsaturated ketone, respectively, as an isostere and fused modified group from ofloxacin (1), and their structures were characterized by elemental analysis and spectral data, and the in vitro antitumor activity against the tested tumor cell lines was evaluated by a MTT assay. RESULTS: Twelve new title compounds were synthesized, and exhibited more significant potency than parent 1. The title compounds with fluorophenyl or O-methoxyphenyl displayed comparable activity to comparasion doxorubicin. CONCLUSION: A fused heterocyclic unsaturated ketone skeleton as an isostere of the C-3 carboxylic acid group are shown to be an alternative route for further design of lead antitumor fluoroquinolone.