Synthesis and antibacterial activity of novel levofloxacin derivatives containing a substituted thienylethyl moiety
Journal Title: DARU Journal of Pharmaceutical Sciences - Year 2012, Vol 20, Issue 0
Abstract
Background and the purpose of the study Piperazinyl quinolones such as ciprofloxacin, ofloxacin and levofloxacin are an important group of quinolone antimicrobials which are widely used in the treatment of various infectious diseases. In the present study, we synthesized a new series of levofloxacin derivatives and evaluated their antibacterial activities.Methods The N-substituted analogs of levofloxacin 6a-j were prepared by nucleophilic reaction of Ndesmethyl 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. Results All compounds showed significant antibacterial activities against Gram-positive bacteria (MIC = 0.04-6.25 mug/mL); however, the activity against Gram-negative bacteria was lower (MIC = 1.56-100 mug/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 mug/mL), and their activities were found to be 5-25 times better than N-desmethyl levofloxacin 11 and equal or better than levofloxacin 4. Conclusion 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 chemotherapy
Authors and Affiliations
Negar Mohammadhosseini, Zahra Alipanahi, Eskandar Alipour, Alireza Foroumadi, Abbass Shafiee, Saeed Emami, Nasrin Samadi, Nika Khoshnevis, Mohammad Ali Faramarzi
Keywords
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