AIM: To evaluate the antiviral potency of a new antihepatitis C virus(HCV) antiviral agent targeting the cellular autophagy machinery. METHODS: Non-infected liver slices, obtained from human liver resection and cut in...AIM: To evaluate the antiviral potency of a new antihepatitis C virus(HCV) antiviral agent targeting the cellular autophagy machinery. METHODS: Non-infected liver slices, obtained from human liver resection and cut in 350 μm-thick slices(2.7 × 106 cells per slice) were infected with cell culture-grown HCV Con1b/C3 supernatant(multiplicity of infection = 0.1) cultivated for up to ten days. HCV infected slices were treated at day 4 post-infection with GNS-396 for 6 d at different concentrations. HCV replication was evaluated by strand-specific real-time quantitative reverse transcription- polymerase chain reaction. The infectivity titers of supernatants were evaluated by foci formation upon inoculation into naive Huh-7.5.1 cells. The cytotoxic effect of the drugs was evaluated by lactate dehydrogenase leakage assays. RESULTS: The antiviral efficacy of a new antiviral drug, GNS-396, an autophagy inhibitor, on HCV infection of adult human liver slices was evidenced in a dosedependent manner. At day 6 post-treatment, GNS-396 EC50 was 158 nmol/L without cytotoxic effect(compared to hydroxychloroquine EC50 = 1.17 μmol/L).CONCLUSION: Our results demonstrated that our ex vivo model is efficient for evaluation the potency of autophagy inhibitors, in particular a new quinoline derivative GNS-396 as antiviral could inhibit HCV infection in a dosedependent manner without cytotoxic effect.展开更多
A novel quinoline derivative 6-(10-thiol-decaoxy ) quinoine (abbreviated as QC10SH )was synthesized and its seif-assembled monoayers (SAMs) were prepared on gold for the first time. Wettability measurement on QC10SH S...A novel quinoline derivative 6-(10-thiol-decaoxy ) quinoine (abbreviated as QC10SH )was synthesized and its seif-assembled monoayers (SAMs) were prepared on gold for the first time. Wettability measurement on QC10SH SAM reveals a hydrophilic surface. RA-IR researches suggests that the SAM has formed highly-organized and closely-packed structure. A method is developed for quanitatively evaluating the molecular orientation in monoayer. By this method the result that the twisting and tilting angles of QC10SH moecule in SAM are 50±4° and 24±3°respectively has been obtained.展开更多
A series of quinoline derivatives was obtained in high yields by an efficient one-pot reaction of substituted o-diiodobenzenes with azazirconacyelopentadienes, which were conveniently prepared from one internal alkyne...A series of quinoline derivatives was obtained in high yields by an efficient one-pot reaction of substituted o-diiodobenzenes with azazirconacyelopentadienes, which were conveniently prepared from one internal alkyne and one nitrile mediated by zirconocene. This proposed synthetic method provides a feasible way to the synthesis of large N-heteroeyclic π-conjugated molecules.展开更多
Inhibition of histone deacetylases (HDACs) is emerging as a new strategy in cancer therapy. In the present work a novel pyrimido-quinoline benzene sulfonamide (PIQSA compound) was designed and synthesized postulating ...Inhibition of histone deacetylases (HDACs) is emerging as a new strategy in cancer therapy. In the present work a novel pyrimido-quinoline benzene sulfonamide (PIQSA compound) was designed and synthesized postulating its ability to inhibit HDAC enzyme in cancer cells. This study was designed to examine the in vitro anti-tumor efficacy of PIQSA against Ehrlich Ascite carcinoma cells (EAC) and three of the human cancer cell lines (H460), brain (U251) and liver (HepG2). The results of Cytotoxic assays showed that PIQSA exhibited in vitro antitumor activity in a dose dependant manner. The tumor growth delay studies indicating that PIQSA resulted in significant regression in tumor growth, which was more pronounced when PIQSA treatment accompanied with radiation exposure. Also, the efficacy of PIQSA to influence radiation response in Ehrlich solid carcinoma (ESC) tumors was estimated. The results suggest that PIQSA exhibited antitumor activities and strong radioenhancing properties associated with inhibition of HDAC activity, DNA fragmentation followed by apoptotic cell death, preferential cell loss of cells particularly in G1/G0 phase through an apoptotic pathway.展开更多
基金Supported by The Institut National de la Sante et de la Recherche Medicale(INSERM,France)the personal support of Professor Jean-Francois Delfraissy as Director of the French Agency,Agence Nationale de Recherches sur le Sida et les hepatites virales(ANRS)
文摘AIM: To evaluate the antiviral potency of a new antihepatitis C virus(HCV) antiviral agent targeting the cellular autophagy machinery. METHODS: Non-infected liver slices, obtained from human liver resection and cut in 350 μm-thick slices(2.7 × 106 cells per slice) were infected with cell culture-grown HCV Con1b/C3 supernatant(multiplicity of infection = 0.1) cultivated for up to ten days. HCV infected slices were treated at day 4 post-infection with GNS-396 for 6 d at different concentrations. HCV replication was evaluated by strand-specific real-time quantitative reverse transcription- polymerase chain reaction. The infectivity titers of supernatants were evaluated by foci formation upon inoculation into naive Huh-7.5.1 cells. The cytotoxic effect of the drugs was evaluated by lactate dehydrogenase leakage assays. RESULTS: The antiviral efficacy of a new antiviral drug, GNS-396, an autophagy inhibitor, on HCV infection of adult human liver slices was evidenced in a dosedependent manner. At day 6 post-treatment, GNS-396 EC50 was 158 nmol/L without cytotoxic effect(compared to hydroxychloroquine EC50 = 1.17 μmol/L).CONCLUSION: Our results demonstrated that our ex vivo model is efficient for evaluation the potency of autophagy inhibitors, in particular a new quinoline derivative GNS-396 as antiviral could inhibit HCV infection in a dosedependent manner without cytotoxic effect.
文摘A novel quinoline derivative 6-(10-thiol-decaoxy ) quinoine (abbreviated as QC10SH )was synthesized and its seif-assembled monoayers (SAMs) were prepared on gold for the first time. Wettability measurement on QC10SH SAM reveals a hydrophilic surface. RA-IR researches suggests that the SAM has formed highly-organized and closely-packed structure. A method is developed for quanitatively evaluating the molecular orientation in monoayer. By this method the result that the twisting and tilting angles of QC10SH moecule in SAM are 50±4° and 24±3°respectively has been obtained.
基金Supported by the National Natural Science Foundation of China（No.21102099）.
文摘A series of quinoline derivatives was obtained in high yields by an efficient one-pot reaction of substituted o-diiodobenzenes with azazirconacyelopentadienes, which were conveniently prepared from one internal alkyne and one nitrile mediated by zirconocene. This proposed synthetic method provides a feasible way to the synthesis of large N-heteroeyclic π-conjugated molecules.
文摘Inhibition of histone deacetylases (HDACs) is emerging as a new strategy in cancer therapy. In the present work a novel pyrimido-quinoline benzene sulfonamide (PIQSA compound) was designed and synthesized postulating its ability to inhibit HDAC enzyme in cancer cells. This study was designed to examine the in vitro anti-tumor efficacy of PIQSA against Ehrlich Ascite carcinoma cells (EAC) and three of the human cancer cell lines (H460), brain (U251) and liver (HepG2). The results of Cytotoxic assays showed that PIQSA exhibited in vitro antitumor activity in a dose dependant manner. The tumor growth delay studies indicating that PIQSA resulted in significant regression in tumor growth, which was more pronounced when PIQSA treatment accompanied with radiation exposure. Also, the efficacy of PIQSA to influence radiation response in Ehrlich solid carcinoma (ESC) tumors was estimated. The results suggest that PIQSA exhibited antitumor activities and strong radioenhancing properties associated with inhibition of HDAC activity, DNA fragmentation followed by apoptotic cell death, preferential cell loss of cells particularly in G1/G0 phase through an apoptotic pathway.
