Synthesis, antimycobacterial and antibacterial activity of l-[(1R,2S)-2-fluorocyclopropyl]naphthyridone derivatives containing an oxime-functionalized pyrrolidine moiety

Abstract

A series of novel 1-[(1R,2S)-2-fluorocyclopropyl]naphthyridone derivatives 21-24 containing an oxime-functionalized pyrrolidine moiety were designed, synthesized and evaluated for their biological activity. Our results reveal that compounds 21a, 21e and 21j show considerable activity against MTB H37Rv ATCC 27294 (MICs: <0.25 μg/mL) and MDR-MTB 6133 (MICs: 0.03-0.054 μg/mL). The target compounds 21-24 are generally poor against the Gram-negative strains, but 21a-j and 22a-c have potent potency (MICs: <0.008-32 μg/mL) against all of the tested Gram-positive strains including MRSA and MRSE with a few exceptions, and the most active compounds 21d, 21e and 22a-c (MICs: <0.008-32 μg/mL) were found to be comparable to or better than moxifloxacin, and 2->250 times more potent than ciprofloxacin and levofloxacin.

Keywords: Antibacterial activity; Antimycobacterial activity; Fluoroquinolone derivatives; Synthesis.