Novel tricyclic fluoroquinolones,[1,2,4]triazolo[3,4-h][1,8]naphthyridine-8-one-7-carboxylic acid derivatives 4a-4h bearing carrying a functional Mannich-base moiety at the C-8 position,were synthesized and evaluated for their antimicrobial activity.The results showed that some compounds with a piperazine side chain exhibited comparable or better antibacterial activity than comparator cirprofloxacin.Furthermore,the targeted compounds also displayed a broad spectrum of activity against resistant strains including both Gram-negative and Gram-positive bacteria.In particular,compound 4h showed an MIC of 0.25 μg/mL in antibacterial assay against multiple drug-resistant Escherichia coli,which represents an about 30-fold increase of potency compared to ciprofloxacin.Thus,their excellent antibacterial activity against resistant strains suggests that triazole-fused fluoroquinolones warrant further optimization as novel anti-infective chemotherapies. Novel tricyclic fluoroquinolones, [1,2,4] triazolo [3,4-h] [1,8] naphthyridine-8-one-7-carboxylic acid derivatives 4a-4h bearing carrying a functional Mannich-base moiety at the C- 8 position, were synthesized and evaluated for their antimicrobial activity. The results showed that some compounds with a piperazine side chain are showing comparable or better antibacterial activity than comparator cirprofloxacin. Fluorrthermore, the targeted compounds also displayed a broad spectrum of activity against resistant strains including both Gram-negative and Gram-positive bacteria. In particular, compound 4h showed an MIC of 0.25 μg / mL in antibacterial assay against multiple drug-resistant Escherichia coli, which represents an about 30-fold increase of potency compared to ciprofloxacin.Thus, their excellent antibacterial activity against resistant mutant suggests that triazole-fused fluoroquinolones warrant further optimization as novel anti-infective chemotherapies.