PARP [poly(ADP-ribose)polymerase] represents a novel potential target in cancer therapy. It is involved in a DNA repair process by catalyzing the transfer of ADP-ribose units from NAD to a number of its substrate proteins. In this work, a series of novel azaindole derivatives was designed and synthesized. Moreover, 16 target molecules were screened and 8 compounds displayed inhibitory activity against PARP-1. It has been demonstrated that these azaindoles bearing cycloamine substituents at 2-position were active to both PARP-1 and PARP-2.
Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Aza Compounds ; chemical synthesis ; chemistry ; pharmacology ; Indoles ; chemical synthesis ; chemistry ; pharmacology ; Poly (ADP-Ribose) Polymerase-1 ; Poly(ADP-ribose) Polymerases ; metabolism

BACKGROUND/AIMS: This study was performed to compare the prevalence rates of primary antibiotic resistance in Helicobacter pylori (H. pylori) isolates among different regions of Korea. METHODS: H. pylori were isolated from gastric mucosal biopsy specimens of 99 Koreans who lived in Gyeonggi (n=40), Kangwon province (n=40) and Busan (n=19) from April to August in 2008. All the patients had no history of H. pylori eradication therapy. The susceptibilities of the H. pylori isolates to amoxicillin, clarithromycin, metronidazole, tetracycline, azithromycin, ciprofloxacin, levofloxacin, and moxifloxacin were tested according to the agar dilution method. RESULTS: There was a difference in resistance to clarithromycin in three institutes located among Gyeonggi (32.5%), Kangwon province (12.5%) and Busan (42.1%) by One way ANOVA test (p=0.027) and nonparametric Kruskal Wallis test (p=0.027). However, by post-hoc analysis, there was no statistically significant difference among three regions. Similarly, the other 7 antibiotics (amoxicillin, metronidazole, tetracycline, azithromycin, ciprofloxacin, levofloxacin and moxifloxacin) did not show any significant difference. CONCLUSIONS: There was no significant regional difference of the primary antibiotic resistance of H. pylori. However, the included patient number might not be enough for this conclusion demanding further evaluations.
Amoxicillin/pharmacology ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Aza Compounds/pharmacology ; Azithromycin/pharmacology ; Ciprofloxacin/pharmacology ; Clarithromycin/pharmacology ; *Drug Resistance, Bacterial ; Female ; Helicobacter Infections/*epidemiology/microbiology ; Helicobacter pylori/*drug effects/isolation & purification ; Humans ; Male ; Metronidazole/pharmacology ; Microbial Sensitivity Tests ; Middle Aged ; Ofloxacin/pharmacology ; Quinolines/pharmacology ; Republic of Korea/epidemiology ; Tetracycline/pharmacology

BACKGROUND/AIMS: This study was performed to compare the prevalence rates of primary antibiotic resistance in Helicobacter pylori (H. pylori) isolates among different regions of Korea. METHODS: H. pylori were isolated from gastric mucosal biopsy specimens of 99 Koreans who lived in Gyeonggi (n=40), Kangwon province (n=40) and Busan (n=19) from April to August in 2008. All the patients had no history of H. pylori eradication therapy. The susceptibilities of the H. pylori isolates to amoxicillin, clarithromycin, metronidazole, tetracycline, azithromycin, ciprofloxacin, levofloxacin, and moxifloxacin were tested according to the agar dilution method. RESULTS: There was a difference in resistance to clarithromycin in three institutes located among Gyeonggi (32.5%), Kangwon province (12.5%) and Busan (42.1%) by One way ANOVA test (p=0.027) and nonparametric Kruskal Wallis test (p=0.027). However, by post-hoc analysis, there was no statistically significant difference among three regions. Similarly, the other 7 antibiotics (amoxicillin, metronidazole, tetracycline, azithromycin, ciprofloxacin, levofloxacin and moxifloxacin) did not show any significant difference. CONCLUSIONS: There was no significant regional difference of the primary antibiotic resistance of H. pylori. However, the included patient number might not be enough for this conclusion demanding further evaluations.
Amoxicillin/pharmacology ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Aza Compounds/pharmacology ; Azithromycin/pharmacology ; Ciprofloxacin/pharmacology ; Clarithromycin/pharmacology ; *Drug Resistance, Bacterial ; Female ; Helicobacter Infections/*epidemiology/microbiology ; Helicobacter pylori/*drug effects/isolation & purification ; Humans ; Male ; Metronidazole/pharmacology ; Microbial Sensitivity Tests ; Middle Aged ; Ofloxacin/pharmacology ; Quinolines/pharmacology ; Republic of Korea/epidemiology ; Tetracycline/pharmacology

This study is designed to investigate the effects of chinfloxacin hydrochloride (CFX) on the kinetics of HERG K+ channel. Whole cell patch clamp technique was used to record HERG K+ currents from HEK293 cells transiently transfected with cgi-HERG-GFP plasmids and channel kinetics were assessed in the absence and presence of CFX and moxifloxacin hydrochloride (MOX). Results demonstrated that the open state of HERG K+ channel was inhibited by CFX in a concentration- and time-dependent manner, with an IC50 of 162.1 +/- 14.2 micromol x L(-1), two folds higher than its positive control MOX. But there were no significant effects on channel kinetics. In addition, the inhibitory effect of CFX on HERG was enhanced when cells were subjected to altered extracellular K+ concentration.
Anti-Bacterial Agents ; administration & dosage ; chemistry ; pharmacology ; Aza Compounds ; pharmacology ; Dose-Response Relationship, Drug ; Ether-A-Go-Go Potassium Channels ; antagonists & inhibitors ; physiology ; Fluoroquinolones ; administration & dosage ; chemistry ; pharmacology ; HEK293 Cells ; Humans ; Inhibitory Concentration 50 ; Kinetics ; Molecular Structure ; Patch-Clamp Techniques ; Potassium ; pharmacology ; Quinolines ; pharmacology ; Time Factors ; Transfection

AIMTo test the antiepileptic effect of phencynonate hydrochloride and investigate its antiepileptic mechanism.

METHODSThrough establishment of different epilepsy models, antiepileptic effects of phencynonate hydrochloride and other drugs were examined. Besides, the effect of phencynonate hydrochloride and other compounds against NMDA-induced lethality in mice, NMDA-induced injury in rat primary hippocampal neuronal cultures and NMDA-induced current were also observed.

RESULTSPhencynonate hydrochloride produced a significant anticonvulsant effect on different epilepsy models. Furthermore, phencynonate hydrochloride also exerted its obvious protection against the lethal effects of NMDA in mice, antagonized the NMDA-induced injury in rat primary hippocampal neuronal cultures and blocked NMDA-induced current in a dose-dependent manner.

CONCLUSIONPhencynonate hydrochloride had a notable anticonvulsant effect on typical epilepsy models, its antiepileptic mechanism might relate to its antagonism against NMDA receptor.

Animals ; Animals, Newborn ; Anticonvulsants ; pharmacology ; therapeutic use ; Aza Compounds ; pharmacology ; therapeutic use ; Cells, Cultured ; Electroshock ; Female ; Glycolates ; pharmacology ; therapeutic use ; Hippocampus ; cytology ; Lethal Dose 50 ; Male ; Mice ; N-Methylaspartate ; toxicity ; Neurons ; drug effects ; Neuroprotective Agents ; pharmacology ; Pentylenetetrazole ; Rats ; Rats, Wistar ; Seizures ; chemically induced ; drug therapy