Author/Authors :
Mohammadhosseini, Negar tehran university of medical sciences tums - Faculty of Pharmacy, Pharmaceutical Sciences Research Center - Department of Medicinal Chemistry, تهران, ايران , Mohammadhosseini, Negar islamic azad university - Department of Chemistry, ايران , Alipanahi, Zahra islamic azad university - Department of Chemistry, ايران , Alipour, Eskandar islamic azad university - Department of Chemistry, ايران , Emami, Saeed mazandaran university of medical sciences - Faculty of Pharmacy, Pharmaceutical Sciences Research Center - Department of Medicinal Chemistry, ايران , Faramarzi, Mohammad Ali tehran university of medical sciences tums - Faculty of Pharmacy - Department of Pharmaceutical Biotechnology, تهران, ايران , Samadi, Nasrin tehran university of medical sciences tums - Faculty of Pharmacy - Department of Pharmaceutical Biotechnology, تهران, ايران , Khoshnevis, Nika tehran university of medical sciences tums - Faculty of Pharmacy - Department of Pharmaceutical Biotechnology, تهران, ايران , Shafiee, Abbass tehran university of medical sciences tums - Faculty of Pharmacy, Pharmaceutical Sciences Research Center - Department of Medicinal Chemistry, تهران, ايران , Foroumadi, Alireza tehran university of medical sciences tums - Faculty of Pharmacy, Pharmaceutical Sciences Research Center - Department of Medicinal Chemistry, تهران, ايران
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 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. Results: 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. 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
Keywords :
Antibacterial activity , Quinolones , Levofloxacin , Thiophene derivatives , Oximes
