J Med Chem：上海药物所报道抗万古霉素耐药菌候选药物

2018-01-05 佚名上海药物所

<div>近日，中国科学院上海药物研究所黄蔚课题组与蓝乐夫课题组在ACS期刊《医药化学杂志》（Journal of Medicinal Chemistry）发表了题为“Extra sugar on vancomycin： new analogues for combating multidrug-resistant Staphylococcus aureus and vancomycin-resistant Enterococci”文章，<span>报道了新型糖肽<a class="channel_keylink" href="http://www.medsci.cn/guideline/list.do?q=%E6%8A%97%E7%94%9F%E7%B4%A0" target="_blank">抗生素</a>衍生物，针对多重耐药的金黄色葡萄球菌和粪肠球菌抗菌活性高于万古霉素128-1024倍。</span></div><div><br></div><div>细菌的<a class="channel_keylink" href="http://www.medsci.cn/guideli

近日，中国科学院上海药物研究所黄蔚课题组与蓝乐夫课题组在ACS期刊《医药化学杂志》（Journal of Medicinal Chemistry）发表了题为“Extra sugar on vancomycin： new analogues for combating multidrug-resistant Staphylococcus aureus and vancomycin-resistant Enterococci”文章，报道了新型糖肽抗生素衍生物，针对多重耐药的金黄色葡萄球菌和粪肠球菌抗菌活性高于万古霉素128-1024倍。

细菌的抗生素耐药已经成为日益严峻的全球公共卫生问题，各种耐药的“超级细菌”威胁着人类健康与生命。近年来世界卫生组织多次发布报告指出，目前新抗生素的研发严重不足，难以面对日趋严峻的耐药菌感染威胁。很多国家和机构开始采取激励措施，鼓励新型抗(耐药)菌药物的研发。糖肽类抗生素万古霉素曾被誉为人类对付超级细菌MRSA（Methecillin-resistant S.aureus）的“终极抗生素”，然而，2002年后出现了万古霉素中度耐药（Vancomycin-intermediate S.aureus，VISA）和完全耐药（Vancomycin-resistant S.aureus，VRSA）的菌株。此外，在世界范围内，万古霉素耐药的肠球菌（Vancomycin-resistant Enterococci，VRE）对人类的威胁也日益加剧。针对国内感染病例数据的分析显示，每年多重耐药的MRSA、VRSA、VRE等耐药菌感染人群达1000万以上，研发新型抗耐药菌新药迫在眉睫。

针对万古霉素耐药机制，文章在万古霉素结构基础上通过引入疏水基团增加耐药菌细胞膜通透性，同时引入糖结构片段促进药物与细菌细胞壁肽聚糖前体配体的结合，显着增强抗耐药菌效果，MIC降低了2-3个数量级。在成药性方面，合理的结构修饰在体内药代和安全性评价方面均表现出良好的优势，疏水基团延长了药物的半衰期、提高了AUC，同时亲水糖结构调控了体内清除率，避免了积蓄毒性。优选化合物SM-V-61大鼠药代显示其半衰期为万古霉素的5倍，AUC为万古霉素的15倍。在安全性方面，SM-V-61的肝肾细胞毒性均小于万古霉素。大鼠急毒实验显示，在药效剂量40倍下无明显不良反应。目前该项目正在进行系统性临床前评价，为临床申报做准备。

该研究项目获得中组部“青年***”计划、国家自然科学基金、中科院药物创新研究院“自主部署项目”资助。

原始出处：

Guan D，et al.，Extra Sugar on Vancomycin： New Analogues for Combating Multidrug-Resistant Staphylococcus aureus and Vancomycin-Resistant Enterococci.J Med Chem. 2018 Jan 2.

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2018-04-12 楚钟

#上海药物所#

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2018-06-30 yuanming7

#候选药物#

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2018-01-15 半夏微凉

学习了谢谢分享

68 0
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2018-01-07 xiaoshitou

#耐药菌#

24 0
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2018-01-07 ms3994565386320060

#Med#

26 0
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topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/oLAjfB7s1ib3IzoRn621JdKCFUI4XvNELcibocrAVU6aUzEVDSaf3rYH08PUYUiagGqxAEhj8g9WqqNvD1CupIpCrmnR2OrqHZh/0, createdBy=7f181365728, createdName=飛歌, createdTime=Sat Jan 06 00:07:37 CST 2018, time=2018-01-06, status=1, ipAttribution=)]
2018-01-07 jyzxjiangqin

万古霉素耐药菌.

71 0
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2018-01-07 虈亣靌

学习了.谢谢分享

54 0
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2018-01-06 1dd8c52fm63(暂无匿称)

学习学习.了解了解

58 0
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2018-01-06 wqkm

^_^^_^^_^^_^^_^

68 0
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replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=93f31631454, createdName=1dd8c52fm63(暂无匿称), createdTime=Sat Jan 06 16:48:57 CST 2018, time=2018-01-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=276056, encodeId=13d92e605624, content=^_^^_^^_^^_^^_^, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/Swp2ehfHpiciczeTntUyQOlIGMzQ705ic67sdMTVMbwTv7KbmlUvxrGvRSvQZjPkz7ib5tEDfIaORgczPtmHDpwojg/0, createdBy=c54b2163125, createdName=wqkm, createdTime=Sat Jan 06 16:42:23 CST 2018, time=2018-01-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=275853, encodeId=a9a82e585329, content=不错学习了很有用, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/oLAjfB7s1ib3IzoRn621JdKCFUI4XvNELcibocrAVU6aUzEVDSaf3rYH08PUYUiagGqxAEhj8g9WqqNvD1CupIpCrmnR2OrqHZh/0, createdBy=7f181365728, createdName=飛歌, createdTime=Sat Jan 06 00:07:37 CST 2018, time=2018-01-06, status=1, ipAttribution=)]
2018-01-06 飛歌

不错学习了很有用

21 0