Synthesis and in-vitro antibacterial activity of/N-piperazinyl quinlone derivatives with 5-chloro-2-thienyl group

Fluoroquinolones are an important group of antimicrobial agents that are used widely in the treatment of various infectious diseases. The purpose of the present study was to synthesize new N-piperazinyl quinolone derivatives with 5-chloro-2-theinyl group having possible antimicrobial activity. Reaction of ciprofloxacin [1], norfloxacin [2] and enoxacin [3] with alpha-bromoketone 10 or alpha-bromooxime derivatives 11a-c in DMF, in the presence of NaHCO[3] at room temperature, afforded corresponding ketones 4a-c or oxime derivatives 5-7[a-c], respectively. The synthesized compounds were tested against a series of Gram-positive and Gram-negative bacteria. The results of MIC tests against both Gram-positive and Gram-negative bacteria revealed that ciprofloxacin derivatives [compounds 4a, 5a, 6a and 7a] were more active than norfloxacin and enoxacin analogues. Compound 5a, containing N-[2-[5-chlorothiophen-2-yl]-2-hydroxyiminoethyl] residue provided a high in vitro antibacterial activity against Gram-positive bacteria, with MIC of 0.06, 0.125, 0.5 and 0.125 micro g/mL against S. aureus, S. epidermidis, E. feacalis and B. subtilis, respectively. Its activity was found to be 4 to 8 times better than reference drug [ciprofloxacin] against all Gram-positive bacteria with the exception of E. feacalis

[In vitro cytotoxicity evaluation of sixteen new n-piperazinyl quinolone derivatives against a panel of tumor cell lines]

Fluoroquinolones are potent inhibitors of bacterial topoisomerase II. They can also inhibit eukaryotic topoisomerase, and may confer antitumoral properties. In this study the antitumoral activity of a new series of N-substituted piperazinyl- fluoroquinolones against a panel of human tumor cell lines was determined by MTT assays. Among the tested compounds N-[2- [5-bromo-2-thienyl]-2-oxoethyl] [C1,N1,E1], N-[2- [5-bromo-2-thienyl]-2-[hydroxyimino] ethyl][C2,N2,E2] and N-[2-[5-bromo-2-thienyl]-2-[phenylmethoxyimino] ethyl] [C3,N3,E3] piperazinyl quinolones exhibited the most cytotoxic activities [mean IC50s = 2.5 to 3 microg/ml], comparable to that of the Etoposide [mean IC50= 1.7micro g/ml]. Replacement of the 5- bromo-2-thienyl with 4- fluorophenyl or 2, 6- difluorophenyl rings leads to variable inhibition activity. The quinolone activity was enhanced by the presence of a chlorine and two fluorine atoms at the benzyl and phenyl groups, especially against ACHN renal adenocarcinoma cell line. These data suggest that these series of quinolones provide good models for the further design of potent antitumor compounds

In Vitro study of cytotoxic effects of new Norfloxacin derivatives on humancancer cell lines

In this in vitro study a series of new norfloxacin derivatives with an oxime or a substituted oxime attached to the piperazine ring at C-7 position were evaluated for their cytotoxicity on Human Cancer Cell Lines. The growth inhibitory activity of these compounds was determined for human cancer cell lines including bladder carcinoma [EJ138], renal adenocarcinoma [ACHN], breast adenocarcinoma [MCF-7], hepatocyte carcinoma [HEPG2], lung carcinoma [A549] and rat-Adrenal fibroblast-pheochromocytoma [PC-12] using colorimetric MTT assay. The results showed that the norfloxacin derivatives tested in this study showed significant inhibitory activity for cancer cell lines. Some of the compounds such as Cl, C9, CIO and Cll exhibited the most inhibitory activity against MCF-7 and PC-12 with IC50 value of 9 microM [p<0.05]. Among the cell lines tested, PC-12 was very sensitive to these compounds. The known cytotoxic drug, Etoposide, demonstrated the most significant activities against all the cell lines tested with IC50 value less than 1.7 microM [p<0.00l]. The results indicated that the synthesized norfloxacin derivatives tested in this study, although they act mostly as antibacterial agents, they can also affect the function of the type 2 DNA topoisomerase in eukaryotic cells. Further studies are needed to elucidate the mechanisms by which these derivatives act

[Antidepressant effect of sour orange flowers extract on lipopolysaccharide-induced depressive-like behaviors in rat]

Based on the documents in traditional medicine regarding the therapeutic effect of Sour orange flowers [Citrus aurantium L.] on the nervous system disorders, this experimental study was conducted to evaluate the pretreatment of Sour orange flowers extract in preventing or reducing depressive-like behaviors induced by systemic injection of lipopolysaccharide [LPS] in rats. To perform this study, percolated extract of sour orange flowers was used. Each experimental group of animals was pretreated with the extract along with drinking water before the injection of LPS. The depressive-like behaviors induced by the injection of LPS consisted of the reduction in the preference for sucrose solutions, food consumption, body weight and inability to pleasure. The LPS-injected rats that were chronically pretreated with the extract improved sucrose preference compared with control group, however this was not significant. Food consumption in extract-pretreated group was significantly increased on day 2 and 3 after the injection of LPS compared with control group [P<0.05]. The effect of extract and LPS on social interaction [consisting of body sniffing and grooming] showed that in extract pretreated rats, the time spent for social interaction was equal to that before the injection [baseline]. However in control group there was a significant reduction in the time spent for social interaction compared to the baseline. Considering the effect of LPS in reduction of neurotransmitters such as serotonin and norepinephrine, the attenuation of Sour orange flowers extract on the effect of LPS might be the result of the effect of extract in increasing the level of this neurotransmitter at their site of the activity. To confirm this, more studies to evaluate the pharmacological effect of extract are required