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.

中文翻译：

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新型[1,2,4]三唑[3,4-h] [1,8]萘啶-7-羧酸衍生物的合成及抑菌活性

新型三环氟喹诺酮类[1,2,4]三唑并[3,4-h] [1,8]萘啶-8-one-7-羧酸衍生物4a - 4h在C-上带有官能曼尼希碱基部分合成8个位置并评估其抗菌活性。结果表明，一些具有哌嗪侧链的化合物表现出与比较剂环丙沙星相当或更好的抗菌活性。此外，目标化合物还对包括革兰氏阴性菌和革兰氏阳性菌在内的抗性菌株表现出广谱的活性。尤其是，化合物4h在针对多种耐药性大肠杆菌的抗菌测定中显示的MIC为0.25μg/ mL与环丙沙星相比，它的效价提高了约30倍。因此，它们对耐药菌株的优异抗菌活性表明，与三唑融合的氟喹诺酮类药物有待进一步优化，作为新型的抗感染化学疗法。