我国抗乙肝新药已开始临床研究

心灵鸡汤

我国抗乙肝新药已开始临床研究

可同时抗乙肝和艾滋病

据新华社电 中国国内第一个具有自主知识产权、能够同时抗乙型肝炎病毒和艾滋病病毒的化学药物“二咖啡酰奎尼酸”已经开始一期临床研究，有望为中国治疗乙型肝炎和艾滋病开辟新途径。负责主持研发该药的军事医学科学院放射和辐射医学研究所董俊兴教授从1994年开始该药的研发，随后发现其同时具有较强的抗乙型肝炎病毒和艾滋病病毒作用。“‘二咖啡酰奎尼酸’临床前试验效果好，毒副作用低，如果临床研究成功，这将是中国医药界的一颗重磅炸弹”董俊兴教授20日在接受记者采访时说。抗艾滋病病毒体内外试验表明，该药具有显著抑制HIV整合酶的作用，能显著抑制病毒复制，延缓或逆转艾滋病变，而现有的“鸡尾酒”疗法仅能延缓病变。“如果在人身上获得同样效果，这将在很大程度上延缓艾滋病病人的生命。”董俊兴教授说。同时，抗“乙肝”病毒的试验发现，该药能显著抑制抗原的产生和病毒DNA复制，作用比现有治疗“乙肝”药物更为持久。董俊兴教授介绍说，“二咖啡酰奎尼酸”是经过大量筛选分离得到的，主要存在于旋覆花、金银花、菊花等抗病毒中草药和咖啡、苦丁茶、葵花子、土豆、茼蒿等水果蔬菜中，现已实现化学合成。据了解，该药已获得中国、美国和欧洲等过发明专利授权，于近日获得国家食品药品监督管理局颁发的两个化学药物一类新药临床研究批文，并在302医院进行一期临床研究。

摘自2006年02月21日《厦门晚报》

[此贴子已经被作者于2006-2-22 19:58:00编辑过]

cqyds

还是继续抗病毒?而不是彻底治愈?[em01]

tonychant

通过PUBMED,我检索到关于这种 药物 下面三篇文章

1

Antiviral Res. 2005 Oct;68(1):1-9.

Related Articles, &lt;SCRIPT language=JavaScript1.2&gt;<br> <!-- var PopUpMenu2_LocalConfig_jsmenu3Config = [ ["ShowCloseIcon","yes"], ["Help","window.open('/entrez/query/static/popup.html','Links_Help','resizable=no,scrollbars=yes,toolbar=no,location=no,directories=no,status=no,menubar=no,copyhistory=no,alwaysRaised=no,depend=no,width=400,height=500');"], ["TitleText"," Links "] ] var jsmenu3Config = [ ["UseLocalConfig","jsmenu3Config","",""] ] //--> </SCRIPT> <SCRIPT language=JavaScript1.2> <!-- var Menu16140400 = [ ["UseLocalConfig","jsmenu3Config","",""], ["Books","window.top.location='http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=16140400&dopt=Books'","",""], ["LinkOut","window.top.location='http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=16140400&dopt=ExternalLink'","",""] ] //--> <br>&lt;/script&gt; 复制代码 Links

Antiviral activity and mode of action of caffeoylquinic acids from Schefflera heptaphylla (L.) Frodin.

Li Y, But PP, Ooi VE.

Department of Chemistry, Jinan University, Guangzhou, China.

Schefflera heptaphylla is a popular medicinal plant in southern China. Three caffeoylquinic acid derivatives, namely 3,4-di-O-caffeoylquinic acid, 3,5-di-O-caffeoylquinic acid, and 3-O-caffeoylquinic acid, were isolated from this plant and investigated for their antiviral activity against respiratory syncytial virus (RSV). 3,4-Di-O-caffeoylquinic acid and 3,5-di-O-caffeoylquinic acid possessed potent anti-RSV activity. The median inhibitory concentrations (IC50) of 3,4-di-O-caffeoylquinic acid and 3,5-di-O-caffeoylquinic acid against RSV were 2.33 microM (1.2 microg/ml) and 1.16 microM (0.6 microg/ml), respectively, in a plaque reduction assay. The dicaffeoylquinic acids exhibited minimal cytotoxicity against HEp-2 cells with median cytotoxic concentration (CC50) higher than 1000 microM. The maximal non-cytotoxic concentration (MNCC) of the two dicaffeoylquinic acids were about 96.7 microM, which suggested their anti-RSV effect was not due to cytotoxicity. The antiviral action of 3,4-di-O-caffeoylquinic acid and 3,5-di-O-caffeoylquinic acid was specific against RSV, as they had no obvious antiviral activity against influenza A (Flu A), Coxsackie B3 (Cox B3), and Herpes simplex type one (HSV-1) viruses. Studies were performed that indicated that the dicaffeoylquinic acids could inhibit RSV directly, extracellularly, but only at much higher concentrations than seen in standard assays. Moreover, they could not inhibit RSV attachment to host cells, and could not protect HEp-2 cells from RSV infection at lower concentrations. The data suggest that the compounds exerted their anti-RSV effects via the inhibition of virus-cell fusion in the early stage, and the inhibition of cell-cell fusion at the end of the RSV replication cycle.

tonychant

Mol Pharmacol. 1997 Dec;52(6):1041-55.

Related Articles, &lt;SCRIPT language=JavaScript1.2&gt;<br> <!-- var Menu9415714 = [ ["UseLocalConfig","jsmenu3Config","",""], ["Compound","window.top.location='http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Display&dopt=pubmed_pccompound&from_uid=9415714'","",""], ["Compound via MeSH","window.top.location='http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Display&dopt=pubmed_pccompound_mesh&from_uid=9415714'","",""], ["Substance","window.top.location='http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Display&dopt=pubmed_pcsubstance&from_uid=9415714'","",""], ["Substance via MeSH","window.top.location='http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Display&dopt=pubmed_pcsubstance_mesh&from_uid=9415714'","",""], ["Cited in PMC","window.top.location='http://www.pubmedcentral.gov/tocrender.fcgi?action=cited&tool=pubmed&pubmedid=9415714'","",""], ["Books","window.top.location='http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=9415714&dopt=Books'","",""], ["LinkOut","window.top.location='http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=9415714&dopt=ExternalLink'","",""] ] //--> <br>&lt;/script&gt; 复制代码 Links

Potent inhibitors of human immunodeficiency virus type 1 integrase: identification of a novel four-point pharmacophore and tetracyclines as novel inhibitors.

Neamati N, Hong H, Sunder S, Milne GW, Pommier Y.

Laboratory of Molecular Pharmacology, National Cancer Institute, Bethesda, Maryland 20892, USA.

A four-point pharmacophore was constructed from energy-minimized structures of chicoric acid and dicaffeoylquinic acid. The search of 206,876 structures in the National Cancer Institute 3D database yielded 179 compounds that contain this pharmacophore. Thirty-nine of these compounds were tested in an in vitro assay specific for human immunodeficiency virus type 1 integrase (IN). Each retrieved structure was fit to the pharmacophore, and the conformation that afforded the best fit was identified. Twenty of the 39 compounds tested exhibited IC50 values of < 20 microM. Among the most potent inhibitors, tetracyclines emerged as a new class of inhibitors. Although the parent tetracycline exhibited marginal potency against purified IN, all substituted tetracyclines tested showed 5-100-fold increased potency. Disintegration assays with truncated IN mutants indicated that tetracyclines inhibit the IN catalytic core domain. To investigate whether chelation of divalent metals is implicated in differential potency of tetracyclines, enzyme assays were performed in the presence of both Mn2+ or Mg2+; no significance difference in potency was observed. Rolitetracycline inhibited IN/DNA complex formation in the presence of EDTA, which suggests that inhibition was metal independent. Rolitetracycline reversed DNA binding of IN after the complex was allowed to form before the addition of drug. Selectivity of tetracyclines was also examined in an assay specific for topoisomerase I, and none of the tetracyclines tested induced topoisomerase I-mediated cleavable complex or inhibited camptothecin-induced cleavable complex. Remarkable potency against the IN in the absence of divalent metals and the core enzyme coupled with water solubility makes tetracyclines potential candidates for X-ray crystal structure determination with IN.

tonychant

Mol Pharmacol. 1996 Oct;50(4):846-55.

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Dicaffeoylquinic acid inhibitors of human immunodeficiency virus integrase: inhibition of the core catalytic domain of human immunodeficiency virus integrase.

Robinson WE Jr, Cordeiro M, Abdel-Malek S, Jia Q, Chow SA, Reinecke MG, Mitchell WM.

Department of Pathology, University of California, Irvine 92697-4800, USA. [email protected]

Integration of a cDNA copy of the human immunodeficiency virus (HIV) genome is mediated by an HIV-1-encoded enzyme, integrase (IN), and is required for productive infection of CD4+ lymphocytes. It had been shown that 3,5-dicaffeoylquinic acid and two analogues were potent and selective inhibitors of HIV-1 IN in vitro. To determine whether the inhibition of IN by dicaffeoylquinic acids was limited to the 3,5 substitution, 3,4-, 4,5-, and 1,5-dicaffeoylquinic acids were tested for inhibition of HIV-1 replication in tissue culture and inhibition of HIV-1 IN in vitro. All of the dicaffeoylquinic acids were found to inhibit HIV-1 replication at concentrations ranging from 1 to 6 microM in T cell lines, whereas their toxic concentrations in the same cell lines were > 120 microM. In addition, the compounds inhibited HIV-1 IN in vitro at submicromolar concentrations. Molecular modeling of these ligands with the core catalytic domain of IN indicated an energetically favorable reaction, with the most potent inhibitors filling a groove within the predicted catalytic site of IN. The calculated change in internal free energy of the ligand/IN complex correlated with the ability of the compounds to inhibit HIV-1 IN in vitro. These results indicate that the dicaffeoylquinic acids as a class are potent and selective inhibitors of HIV-1 IN and form important lead compounds for HIV drug discovery.

轻舟一叶

无论也是希望！感谢那些日夜工作的研究人员！战友们坚持下去！有好消息请大家一定及时告之！

心灵鸡汤

黎明前的黑暗！曙光即将到来了！战友们顶住！！

阳先生

对中国绝望！

心灵鸡汤

大家应该不要放弃任何一次希望！即使是渺茫的。

曾经沧海11

看来我们的生活还是充满阳光，生命不会因此而终止[em02][em02]

但愿国产的有自主知识产权的管用的新药及早上市

[em05][em05]