A series of novel (R)/(S)-7-(3-alkoxyimino-2-aminomethyl-1-azetidinyl)fluoroquinolone derivatives were synthesized and evaluated for their in vitro antibacterial activity against representative strains. Our results reveal that 12 of the target compounds generally show better activity (MIC: <0.008–0.5 μg mL⁻¹) against the tested Gram-positive strains including MRSA and MRSE than levofloxacin (LVFX, MIC: 0.125–8 μg mL⁻¹). Their activity is similar to that of gemifloxacin (GMFX, MIC: <0.008–4 μg mL⁻¹). However, they are generally less active than the two reference drugs against Gram-negative strains. Moreover, against clinical strains of S. aureus including MRSA and S. epidermidis including MRSE, the MIC₅₀ values (0.06–16 μg mL⁻¹) and MIC₉₀ values (0.5–32 μg mL⁻¹) of compounds 16 w, y, and z are 2–8- and 2–16-fold less than LVFX, respectively, and 16 w (MIC₉₀ range: 0.5–4 μg mL⁻¹) was also found to be more active than GMFX (MIC₉₀ range: 1–8 μg mL⁻¹).

A series of gatifloxacin, ciprofloxacin, and 8-OCH₃ ciprofloxacin coumarin derivatives with remarkable improvement in lipophilicity as compared to the parent fluoroquinolones was designed, synthesized, and characterized by ¹H-NMR, MS, and HRMS. These derivatives were evaluated for their in-vitro activity against Mycobacterium smegmatis CMCC 93202 and MTB H37Rv ATCC 27294. All of the synthesized compounds were less active than the parent compounds against M. smegmatis CMCC 93202, but the activity of compound 6 was found to be 2–8-fold more potent than ciprofloxacin, 8-OCH₃ ciprofloxacin, moxifloxacin, and rifampin, and comparable to gatifloxacin against MTB H37Rv ATCC 27294. These results indicated that the lipophilicity of the tested compounds is not the sole parameter affecting antimycobacterial activity.

A series of novel 7-(3-alkoxyimino-4-methyl-4-methylaminopiperidin-1-yl)fluoroquinolone derivatives were designed, synthesized, and characterized by ¹H-NMR, MS, and HRMS. These fluoroquinolones were evaluated for their in-vitro antibacterial activity against representative Gram-positive and Gram-negative strains. Generally, all of the target compounds have considerable antibacterial activity against the tested forty strains, and exhibit exceptional potency in inhibiting the growth of methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) ATCC33591 (MICs: 0.06 to 2 μg/mL). In particular, compounds 14, 19, 28, and 29 are fourfold more potent than ciprofloxacin against MSSA 08-49. Compounds 23, 26, and 27 are twofold more potent than ciprofloxacin against MRSA ATCC33591 and MSSA ATCC29213. In addition, compound 14 exhibits excellent activity (MIC: 0.06 μg/mL) against Acinetobactes calcoaceticus, which is two- to 16-fold more potent than the reference drugs gemifloxacin, levofloxacin, and ciprofloxacin.