Novel N-2-(Furyl)-2-(chlorobenzyloxyimino) ethyl Piperazinyl Quinolones: Synthesis, Cytotoxic Evaluation and Structure-activity Relationship

Document Type: Research article

Authors

1 Young Researchers and Elite Club, Islamshahr Branch, Islamic Azad University, Tehran, Iran

2 Institute of Biochemistry and Biophysics, University of Tehran, PO Box 13145-1384, Tehran, Iran

3 Biotechnology Department, Iranian Research Organization for Science and Technology (IROST), Tehran, Iran

4 Drug Design & Development Research Center, Tehran University of Medical Sciences, Tehran 14176, Iran

5 School of Chemistry, University College of Science, University of Tehran, P.O. Box 14155-6455, Tehran, Iran

6 Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

7 Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14176, Iran

8 Drug Design and Development Research Center, Tehran University of Medical Sciences, Tehran, Iran

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.

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