7-Piperazinylquinolones with methylene-bridged nitrofuran scaffold as new antibacterial agents
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Med Chem Res (2013) 22:5940–5947 DOI 10.1007/s00044-013-0581-9
ORIGINAL RESEARCH
7-Piperazinylquinolones with methylene-bridged nitrofuran scaffold as new antibacterial agents Saeed Emami • Nima Shahrokhirad • Alireza Foroumadi • Mohammad Ali Faramarzi • Nasrin Samadi • Narges Soltani-Ghofrani
Received: 2 December 2012 / Accepted: 11 March 2013 / Published online: 28 March 2013 Ó Springer Science+Business Media New York 2013
Abstract Quinolone class of antibacterial agents has considerable attention to find new useful antibacterial agents. Therefore, a series of N-substituted piperazinylquinolones bearing (5-nitrofuran-2-yl)methyl moiety were synthesized and evaluated against a variety of bacteria. The methylene-bridged nitrofuran functionality has been recently used in oxazolidinone class of antibacterial agents containing piperazinyl moiety by introducing ranbezolid as a 5-nitrofuran analog of eperzolid. The results of antibacterial evaluation revealed that the influence of (5-nitrofuran-2-yl) attachment to the 7-piperazinylquinolones against different bacterial species depends on the type of substituents at the N-1 and C-8 positions. Better results were obtained with ethyl at N-1 and CF at C-8 in the term of activity against Bacillus subtilis and E. coli. While, the optimum activity against Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumonia was entailed
S. Emami (&) N. Shahrokhirad Department of Medicinal Chemistry and Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran e-mail: [email protected] A. Foroumadi Department of Medicinal Chemistry, Faculty of Pharmacy and Drug Design and Development Research Center, Tehran University of Medical Sciences, Tehran, Iran M. A. Faramarzi N. Soltani-Ghofrani Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran N. Samadi Department of Drug and Food Control, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
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by a molecule possessing cyclopropyl at N-1 and CH at C-8. Keywords Antibacterial activity Quinolones 5-Nitrofuran Structure–activity relationship
Introduction Quinolones are an important class of chemotherapeutic agents, which are widely used for the treatment of various bacterial infections in both community and hospital settings due to their broad spectrum and excellent oral bioavailability (Mugnaini et al., 2009; Emami et al., 2005). Quinolones exert their antibacterial action by the inhibition of type II bacterial topoisomerases such as DNA gyrase and topoisomerase IV (Ball, 2000). DNA gyrase is an essential bacterial enzyme responsible for the maintenance of DNA topology by introducing negative supercoils in DNA within transcription and replication processes. Topoisomerase IV provides a potent ATPdependent chromosome decatenation and relaxation activity (Cheng et al., 2007). Therefore, the quinolones by inhibiting these enzymes block the transcription and the DNA replication,
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