title: N-Substituted piperazinyl quinolones as potential cytotoxic agents: structure-activity relationships study.
abstract: As part of a continuing search for new potential anticancer candidates in the piperazinyl quinolone series, the cytotoxicity evaluation of new N-substituted piperazinyl quinolones was of our interest. The growth inhibitory activities of 12 new compounds, namely N-[2-(5-chlorothiophen-2-yl)-2-oxoethyl] and N-[2-(5-chlorothiophen-2-yl)-2-oxyiminoethyl] piperazinyl quinolones 1-12 were determined against six cancer cell lines using MTT colorimetric assay. Preliminary screening showed that most of the new N-[2-(5-chlorothiophen-2-yl)ethyl]piperazinyl quinolones 4-12 containing (un)substituted oxime moiety showed significant cytotoxic activity and the modification of functionality on ethyl spacer produced a relatively minor change of activity. Thus, in the piperazinyl quinolone series, cytotoxic activity can be positively modulated through the introduction of 2-(5-chlorothiophen-2-yl)ethyl residue on the piperazine ring. The results revealed that the introduction of 2-(5-chlorothiophen-2-yl)ethyl moiety on the piperazine ring of quinolone antibacterials (ciprofloxacin, norfloxacin and enoxacin) changes the biological profile of piperazinyl quinolones from antibacterials to cytotoxic agents.
authors.affiliation: Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14174, Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Foroumadi
authors.forename: Saeed
authors.initials: S
authors.lastname: Emami
authors.forename: Saeed
authors.initials: S
authors.lastname: Rajabalian
authors.forename: Marziyeh
authors.initials: M
authors.lastname: Badinloo
authors.forename: Negar
authors.initials: N
authors.lastname: Mohammadhosseini
authors.forename: Abbas
authors.initials: A
authors.lastname: Shafiee
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003124:Colorimetry; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D015363:Quinolones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D015363:Quinolones; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue