RESUMEN
OBJECTIVE: To explore an efficient structure modification route to transform antibacterial fluoroquinolones to antitumor ones. METHODS: Compound A[1,3,4] oxadiazol-5-thiol 3 derived from ofloxacin 1 was subjected to nucleophilic substitution with each of chloromethyl-1,3,4-oxadiazoles 4a-4g gave di-oxadiazolyl methylsulfides 5a-5g, followed by a quaternization to form the corresponding methiodides 6a-6g, respectively. The in vitro antitumor activity of the title compounds 5a-5g and 6a-6g against three cancer cell lines was evaluated by MTT method. RESULTS: Fourteen title compunds were synthesized and the structures were characterized by corresponding spectral data. The bioactive assay showed that compounds 5a-5g and 6a-6g exhibited a potential anticancer activity (IC50 < 25 μmol · L-1). The activity of the quaternary ammoniums 6a-6g was higher than that of the corresponding free bases 5a-5g. CONCLUSION: The design and synthesis of antitumor fluoroquinolone based on antibacterial fluoroquinolone C-3 heterocycle are worthy of further study.
RESUMEN
Objective To develop models of epileptic discharge by activating group Ⅰ metabotropic glutamate receptors (mGluR) or by blocking gamma-aminobutyric acid (GABA) receptors on rat hippocampal slices. Methods Rat hippocampal slices were exposed to mGluR group Ⅰ specific agonist dihydroxyphenylglycine (DHPG) or to GABAA receptor antagonists bicuculline methiodide(BMI), and single pyramidal cell in the CA3 region of the slice was recorded by whole cell patch clamp technique. Results Exposure to DHPG or BMI resulted in the induction of spontaneously occurring epileptic discharge in the CA3 region of rat hippocampal slice, and there was no significant difference in the frequency of discharge between them(P>0.05). Conclusion Epileptic discharge can be generated in vitro in response to a loss of balance between excitatory and inhibitory influences.