title: Novel N-2-(Furyl)-2-(chlorobenzyloxyimino) Ethyl Piperazinyl Quinolones: Synthesis, Cytotoxic Evaluation and Structure-Activity Relationship.
abstract: Quinolone antibacterials are one of the most important classes of pharmacological agents known as potent inhibitors of bacterial DNA gyrase and topoisomerase IV that efficiently inhibit DNA replication and transcription by generating several double-stranded DNA break. Some quinolone derivatives demonstrated inhibitory potential against eukaryote topoismarase II and substantial dose-dependent cytotoxic potential against some cancerous cells. In present study, synthesis and cytotoxic activity evaluation of new series of N-pipearzinyl quinolones containing N-2-(furyl-2 or 3-yl)-2-(chlorobenzyloxyimino) ethyl moiety 7a-i have been studied. Reaction of quinolone, with 2-bromo-1-(furan-2 or 3-yl)ethanone-O-substituted chlorobenzyloxime in DMF in presence of NaHCO3 at room temperature, gave the title compounds N-2-(furan-2 or 3-yl)-2-(chlorobenzyloxyiminoethyl) quinolone 7a-i. Synthesized compounds were further evaluated in-vitro against three human breast tumor cell lines. Preliminary screening indicated that compound 7 g demonstrated significant growth inhibitory potential against all evaluated cell lines. The results of structure-activity relationship study exhibited that quinolone derivatives are superior in cytotoxic potential compared to 1, 8-naphthyridone series. Furthermore, ethyl quinolone derivatives were more potent cytotoxic agents comparing with cyclopropyl quinolones.
authors.affiliation: Young Researchers and Elite Club, Islamshahr Branch, Islamic Azad University, Tehran, Iran.
authors.forename: Negar
authors.initials: N
authors.lastname: Mohammadhosseini
authors.affiliation: Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.
authors.forename: Mahboobeh
authors.initials: M
authors.lastname: Pordeli
authors.affiliation: Biotechnology Department, Iranian Research Organization for Science and Technology (IROST), Tehran, Iran.
authors.forename: Maliheh
authors.initials: M
authors.lastname: Safavi
authors.affiliation: Drug Design and Development Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Loghman
authors.initials: L
authors.lastname: Firoozpour
authors.affiliation: School of Chemistry, University College of Science, University of Tehran, Tehran, Iran.
authors.forename: Fatame
authors.initials: F
authors.lastname: Amin
authors.affiliation: Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.
authors.forename: Sussan
authors.initials: S
authors.lastname: Kabudanian Ardestani
authors.affiliation: Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Najmeh
authors.initials: N
authors.lastname: Edraki
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Abbas
authors.initials: A
authors.lastname: Shafiee
authors.affiliation: Drug Design and Development Research Center, Tehran University of Medical Sciences, Tehran, Iran. ; Department of Medicinal Chemistry, School of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Foroumadi
keywords: Cytotoxic activity; Furyl; N-pipearzinyl quinolones; Structure-activity Relationship