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Front Microbiol: 萘醌衍生物可用于研发新的抗结核药物

2018-05-16 MedSci MedSci原创

尽管结核病是一种可治愈的疾病,但由于其治疗的长期性以及其毒性作用、结核病/艾滋病合并感染以及耐药结核分枝杆菌菌株的出现使得结核病仍然是一个全球的公共卫生问题。继续开发新型抗菌药物,可以减少治疗时间并对易感和耐药菌株有效。醌类化合物是天然来源的化合物,其中萘醌类具有抗真菌、抗寄生虫和抗分支杆菌活性。因此,我们评估了六种1,4-萘醌衍生物的潜在抗分支杆菌活性。我们测定了化合物对三种结核分枝杆菌菌株的最

尽管结核病是一种可治愈的疾病,但由于其治疗的长期性以及其毒性作用、结核病/艾滋病合并感染以及耐药结核分枝杆菌菌株的出现使得结核病仍然是一个全球的公共卫生问题。继续开发新型抗菌药物,可以减少治疗时间并对易感和耐药菌株有效。


醌类化合物是天然来源的化合物,其中萘醌类具有抗真菌、抗寄生虫和抗分支杆菌活性。因此,我们评估了六种1,4-萘醌衍生物的潜在抗分支杆菌活性。

我们测定了化合物对三种结核分枝杆菌菌株的最小抑制浓度(MIC),包括泛易感的H37Rv(ATCC 27294);一种对异烟肼单一抗性(ATCC 35822)和一种对利福平单2一抗性(ATCC 35838)。在J774A.1(ATCC TIB-67)巨噬细胞中评估细胞毒性;在硅片分析中进行关于吸收、分布、代谢和排泄(ADME)和停靠点的研究。

结果显示,萘醌对三株菌都具有抗菌活性,MIC为206.6-12.5μM,且MIC值较低的化合物也显示出低的细胞毒性。此外,两个萘醌衍生物5和6并不显示与异烟肼和利福平的交叉耐药性。ADME分析显示化合物没有违反Lipinski's五规则。

综上所述,该研究结果表明,这些萘醌在研发新的结核治疗策略上具有很好的前景。

原始出处:


Priscila C. B. Halicki, Laís A. Ferreira, et al., Naphthoquinone Derivatives as Scaffold to Develop New Drugs for Tuberculosis Treatment. Front Microbiol. 2018; 9: 673. doi:  10.3389/fmicb.2018.00673.

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createdName=12498ebem31暂无昵称, createdTime=Sat Jun 09 12:48:00 CST 2018, time=2018-06-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1668580, encodeId=5544166858071, content=<a href='/topic/show?id=988c556181c' target=_blank style='color:#2F92EE;'>#抗结核药物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55618, encryptionId=988c556181c, topicName=抗结核药物)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=504a26353164, createdName=wincls, createdTime=Mon Jun 25 23:48:00 CST 2018, time=2018-06-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2084402, encodeId=4c992084402ba, content=<a href='/topic/show?id=61f411e013b' target=_blank style='color:#2F92EE;'>#Micro#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11701, encryptionId=61f411e013b, topicName=Micro)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d59291, createdName=xjy02, createdTime=Sat Feb 02 14:48:00 CST 2019, time=2019-02-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1812669, encodeId=a3171812669f4, content=<a href='/topic/show?id=d193900940b' target=_blank style='color:#2F92EE;'>#衍生物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=90094, encryptionId=d193900940b, topicName=衍生物)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=仁心济世, createdTime=Thu Oct 11 04:48:00 CST 2018, time=2018-10-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1918088, encodeId=128c191808836, content=<a href='/topic/show?id=4f26341994' target=_blank style='color:#2F92EE;'>#Bio#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3419, encryptionId=4f26341994, topicName=Bio)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=12de429, createdName=sunylz, createdTime=Tue Aug 14 18:48:00 CST 2018, time=2018-08-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1857650, encodeId=abf2185e6506a, content=<a href='/topic/show?id=3f48525849' target=_blank style='color:#2F92EE;'>#CRO#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5258, encryptionId=3f48525849, topicName=CRO)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=778d36, createdName=柳叶一刀, createdTime=Sat Dec 15 21:48:00 CST 2018, time=2018-12-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=322425, encodeId=94bf3224255a, content=了解了解.继续关注, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=93f31631454, createdName=1dd8c52fm63(暂无匿称), createdTime=Fri Jun 08 07:42:32 CST 2018, time=2018-06-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1254169, encodeId=1b08125416916, content=<a href='/topic/show?id=f30ae86297d' target=_blank style='color:#2F92EE;'>#结核#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=78629, encryptionId=f30ae86297d, topicName=结核)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4dfa37, createdName=huhuaidong387, createdTime=Fri May 18 03:48:00 CST 2018, time=2018-05-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1300149, encodeId=d6651300149b3, content=<a href='/topic/show?id=ed5ee332423' target=_blank style='color:#2F92EE;'>#研发#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=73324, encryptionId=ed5ee332423, topicName=研发)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=aea0290, createdName=lqvr, createdTime=Fri May 18 03:48:00 CST 2018, time=2018-05-18, status=1, ipAttribution=)]
    2019-02-02 xjy02
  5. [GetPortalCommentsPageByObjectIdResponse(id=1967412, encodeId=069c196e412ba, content=<a href='/topic/show?id=65995561e43' target=_blank style='color:#2F92EE;'>#抗结核药#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55617, encryptionId=65995561e43, topicName=抗结核药)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=80c5136, createdName=drj2003, createdTime=Mon Apr 01 11:48:00 CST 2019, time=2019-04-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1767449, encodeId=62b91e67449d8, content=<a href='/topic/show?id=64f5343e2f' target=_blank style='color:#2F92EE;'>#Biol#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3437, encryptionId=64f5343e2f, topicName=Biol)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=446937890434, 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href='/topic/show?id=4f26341994' target=_blank style='color:#2F92EE;'>#Bio#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3419, encryptionId=4f26341994, topicName=Bio)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=12de429, createdName=sunylz, createdTime=Tue Aug 14 18:48:00 CST 2018, time=2018-08-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1857650, encodeId=abf2185e6506a, content=<a href='/topic/show?id=3f48525849' target=_blank style='color:#2F92EE;'>#CRO#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5258, encryptionId=3f48525849, topicName=CRO)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=778d36, createdName=柳叶一刀, createdTime=Sat Dec 15 21:48:00 CST 2018, time=2018-12-15, status=1, ipAttribution=), 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  6. [GetPortalCommentsPageByObjectIdResponse(id=1967412, encodeId=069c196e412ba, content=<a href='/topic/show?id=65995561e43' target=_blank style='color:#2F92EE;'>#抗结核药#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55617, encryptionId=65995561e43, topicName=抗结核药)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=80c5136, createdName=drj2003, createdTime=Mon Apr 01 11:48:00 CST 2019, time=2019-04-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1767449, encodeId=62b91e67449d8, content=<a href='/topic/show?id=64f5343e2f' target=_blank style='color:#2F92EE;'>#Biol#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3437, encryptionId=64f5343e2f, topicName=Biol)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=446937890434, 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href='/topic/show?id=4f26341994' target=_blank style='color:#2F92EE;'>#Bio#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3419, encryptionId=4f26341994, topicName=Bio)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=12de429, createdName=sunylz, createdTime=Tue Aug 14 18:48:00 CST 2018, time=2018-08-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1857650, encodeId=abf2185e6506a, content=<a href='/topic/show?id=3f48525849' target=_blank style='color:#2F92EE;'>#CRO#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5258, encryptionId=3f48525849, topicName=CRO)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=778d36, createdName=柳叶一刀, createdTime=Sat Dec 15 21:48:00 CST 2018, time=2018-12-15, status=1, ipAttribution=), 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    2018-08-14 sunylz
  7. 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href='/topic/show?id=4f26341994' target=_blank style='color:#2F92EE;'>#Bio#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3419, encryptionId=4f26341994, topicName=Bio)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=12de429, createdName=sunylz, createdTime=Tue Aug 14 18:48:00 CST 2018, time=2018-08-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1857650, encodeId=abf2185e6506a, content=<a href='/topic/show?id=3f48525849' target=_blank style='color:#2F92EE;'>#CRO#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5258, encryptionId=3f48525849, topicName=CRO)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=778d36, createdName=柳叶一刀, createdTime=Sat Dec 15 21:48:00 CST 2018, time=2018-12-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=322425, encodeId=94bf3224255a, content=了解了解.继续关注, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=93f31631454, createdName=1dd8c52fm63(暂无匿称), createdTime=Fri Jun 08 07:42:32 CST 2018, time=2018-06-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1254169, encodeId=1b08125416916, content=<a href='/topic/show?id=f30ae86297d' target=_blank style='color:#2F92EE;'>#结核#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=78629, encryptionId=f30ae86297d, topicName=结核)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4dfa37, createdName=huhuaidong387, createdTime=Fri May 18 03:48:00 CST 2018, time=2018-05-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1300149, encodeId=d6651300149b3, content=<a href='/topic/show?id=ed5ee332423' target=_blank style='color:#2F92EE;'>#研发#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=73324, encryptionId=ed5ee332423, topicName=研发)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=aea0290, createdName=lqvr, createdTime=Fri May 18 03:48:00 CST 2018, time=2018-05-18, status=1, ipAttribution=)]
    2018-12-15 柳叶一刀
  8. [GetPortalCommentsPageByObjectIdResponse(id=1967412, encodeId=069c196e412ba, content=<a href='/topic/show?id=65995561e43' target=_blank style='color:#2F92EE;'>#抗结核药#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55617, encryptionId=65995561e43, topicName=抗结核药)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=80c5136, createdName=drj2003, createdTime=Mon Apr 01 11:48:00 CST 2019, time=2019-04-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1767449, encodeId=62b91e67449d8, content=<a href='/topic/show?id=64f5343e2f' target=_blank style='color:#2F92EE;'>#Biol#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3437, encryptionId=64f5343e2f, topicName=Biol)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=446937890434, 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href='/topic/show?id=4f26341994' target=_blank style='color:#2F92EE;'>#Bio#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3419, encryptionId=4f26341994, topicName=Bio)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=12de429, createdName=sunylz, createdTime=Tue Aug 14 18:48:00 CST 2018, time=2018-08-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1857650, encodeId=abf2185e6506a, content=<a href='/topic/show?id=3f48525849' target=_blank style='color:#2F92EE;'>#CRO#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5258, encryptionId=3f48525849, topicName=CRO)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=778d36, createdName=柳叶一刀, createdTime=Sat Dec 15 21:48:00 CST 2018, time=2018-12-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=322425, encodeId=94bf3224255a, content=了解了解.继续关注, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=93f31631454, createdName=1dd8c52fm63(暂无匿称), createdTime=Fri Jun 08 07:42:32 CST 2018, time=2018-06-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1254169, encodeId=1b08125416916, content=<a href='/topic/show?id=f30ae86297d' target=_blank style='color:#2F92EE;'>#结核#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=78629, encryptionId=f30ae86297d, topicName=结核)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4dfa37, createdName=huhuaidong387, createdTime=Fri May 18 03:48:00 CST 2018, time=2018-05-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1300149, encodeId=d6651300149b3, content=<a href='/topic/show?id=ed5ee332423' target=_blank style='color:#2F92EE;'>#研发#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=73324, encryptionId=ed5ee332423, topicName=研发)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=aea0290, createdName=lqvr, createdTime=Fri May 18 03:48:00 CST 2018, time=2018-05-18, status=1, ipAttribution=)]
    2018-06-08 1dd8c52fm63(暂无匿称)

    了解了解.继续关注

    0

  9. [GetPortalCommentsPageByObjectIdResponse(id=1967412, encodeId=069c196e412ba, content=<a href='/topic/show?id=65995561e43' target=_blank style='color:#2F92EE;'>#抗结核药#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55617, encryptionId=65995561e43, topicName=抗结核药)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=80c5136, createdName=drj2003, createdTime=Mon Apr 01 11:48:00 CST 2019, time=2019-04-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1767449, encodeId=62b91e67449d8, content=<a href='/topic/show?id=64f5343e2f' target=_blank style='color:#2F92EE;'>#Biol#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3437, encryptionId=64f5343e2f, topicName=Biol)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=446937890434, 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  10. 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href='/topic/show?id=4f26341994' target=_blank style='color:#2F92EE;'>#Bio#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3419, encryptionId=4f26341994, topicName=Bio)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=12de429, createdName=sunylz, createdTime=Tue Aug 14 18:48:00 CST 2018, time=2018-08-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1857650, encodeId=abf2185e6506a, content=<a href='/topic/show?id=3f48525849' target=_blank style='color:#2F92EE;'>#CRO#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5258, encryptionId=3f48525849, topicName=CRO)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=778d36, createdName=柳叶一刀, createdTime=Sat Dec 15 21:48:00 CST 2018, time=2018-12-15, status=1, ipAttribution=), 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GetPortalCommentsPageByObjectIdResponse(id=1300149, encodeId=d6651300149b3, content=<a href='/topic/show?id=ed5ee332423' target=_blank style='color:#2F92EE;'>#研发#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=73324, encryptionId=ed5ee332423, topicName=研发)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=aea0290, createdName=lqvr, createdTime=Fri May 18 03:48:00 CST 2018, time=2018-05-18, status=1, ipAttribution=)]
    2018-05-18 lqvr

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