Synthesis and antibacterial activity of novel levofloxacin derivatives containing a substituted thienylethyl moiety

The N-substituted analogs of levofloxacin 6a–j were prepared by nucleophilic reaction of N-desmethyl levofloxacin 11 with thienylethyl bromide derivatives 8 or 9. All target compounds were tested using conventional agar dilution method in comparison to levofloxacin and N-desmethyl levofloxacin and their MIC values were determined against a panel of Gram-positive and Gram-negative bacteria.All compounds showed significant antibacterial activities against Gram-positive bacteria (MIC？=？0.04-6.25 μg/mL); however, the activity against Gram-negative bacteria was lower (MIC？=？1.56–100 μg/mL). As is evident from the data, oxime derivatives 6e, 6h and 6i are superior in inhibiting the growth of Gram-positive bacteria (MIC？=？0.04–0.19 μg/mL), and their activities were found to be 5–25 times better than N-desmethyl levofloxacin 11 and equal or better than levofloxacin 4.We have designed and synthesized novel quinolone derivatives bearing functionalized thienylethyl moiety on the piperazine ring of levofloxacin. The results of antibacterial screening against Gram-positive and Gram-negative bacteria revealed that the introduction of functionalized thienylethyl moiety on the piperazine ring of levofloxacin can improve the activity against Gram-positive bacteria. Gram-positive bacteria are responsible for a wide range of infectious diseases, and rising resistance in this group is causing increasing concern. Thus, this study introduces structural features of levofloxacin scaffold for development of new candidates in the field of anti-Gram positive chemotherapyFluoroquinolones which are synthetic antibacterial agents are useful for the treatment of urinary tract infections, soft tissue infections, respiratory infections, typhoid fever, sexually transmitted diseases, bone-joint infections, community-acquired pneumonia, acute bronchitis, and sinusitis [1]. Fluoroquinolones consist of a bicyclic ring structure in which there is a substitution at position N-1; most of the current agents