5'-O-[N-(水杨基)氨磺酰基]腺苷的2-芳基-8-氮杂-3-脱氮腺苷类似物：阻断结核分枝杆菌中铁载体生物合成的核苷类抗生素。
2-Aryl-8-aza-3-deazaadenosine analogues of 5'-O-[N-(salicyl)sulfamoyl]adenosine: Nucleoside antibiotics that block siderophore biosynthesis in Mycobacterium tuberculosis.
作者信息
Krajczyk Anna, Zeidler Joanna, Januszczyk Piotr, Dawadi Surendra, Boshoff Helena I, Barry Clifton E, Ostrowski Tomasz, Aldrich Courtney C
机构信息
Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, Poland.
Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, USA.
出版信息
Bioorg Med Chem. 2016 Jul 15;24(14):3133-43. doi: 10.1016/j.bmc.2016.05.037. Epub 2016 May 20.
Abstract
A series of 5'-O-[N-(salicyl)sulfamoyl]-2-aryl-8-aza-3-deazaadenosines were designed to block mycobactin biosynthesis in Mycobacterium tuberculosis (Mtb) through inhibition of the essential adenylating enzyme MbtA. The synthesis of the 2-aryl-8-aza-3-deazaadenosine nucleosides featured sequential copper-free palladium-catalyzed Sonogashira coupling of a precursor 4-cyano-5-iodo-1,2,3-triazolonucleoside with terminal alkynes and a Minakawa-Matsuda annulation reaction. These modified nucleosides were shown to inhibit MbtA with apparent Ki values ranging from 6.1 to 25nM and to inhibit Mtb growth under iron-deficient conditions with minimum inhibitory concentrations ranging from 12.5 to >50μM.
摘要
设计了一系列5'-O-[N-(水杨基)氨磺酰基]-2-芳基-8-氮杂-3-脱氮腺苷，旨在通过抑制必需的腺苷酸化酶MbtA来阻断结核分枝杆菌（Mtb）中的分枝杆菌素生物合成。2-芳基-8-氮杂-3-脱氮腺苷核苷的合成特点是前体4-氰基-5-碘-1,2,3-三唑核苷与末端炔烃进行无铜钯催化的Sonogashira偶联反应以及皆川-松田环化反应。这些修饰的核苷显示出对MbtA的抑制作用，其表观Ki值范围为6.1至25nM，并且在缺铁条件下抑制Mtb生长，最低抑菌浓度范围为12.5至>50μM。
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本文引用的文献
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Immunol Rev. 2015 Mar;264(1):288-307. doi: 10.1111/imr.12252.
3
Iron acquisition strategies in mycobacteria.分枝杆菌中的铁获取策略。
Tuberculosis (Edinb). 2015 Mar;95(2):123-30. doi: 10.1016/j.tube.2015.01.004. Epub 2015 Jan 17.
4
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ACS Med Chem Lett. 2013 Dec 12;4(12):1213-7. doi: 10.1021/ml400328a.
5
Pharmacokinetic and in vivo efficacy studies of the mycobactin biosynthesis inhibitor salicyl-AMS in mice.在小鼠体内的药代动力学和疗效研究中，分枝杆菌生物合成抑制剂水杨酰-AMS 的表现。
Antimicrob Agents Chemother. 2013 Oct;57(10):5138-40. doi: 10.1128/AAC.00918-13. Epub 2013 Jul 15.
6
Analyses of MbtB, MbtE, and MbtF suggest revisions to the mycobactin biosynthesis pathway in Mycobacterium tuberculosis.分析 MbtB、MbtE 和 MbtF 表明结核分枝杆菌中的分枝菌酸生物合成途径需要修订。
J Bacteriol. 2012 Jun;194(11):2809-18. doi: 10.1128/JB.00088-12. Epub 2012 Mar 23.
7
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Bioorg Med Chem. 2011 Jul 15;19(14):4386-98. doi: 10.1016/j.bmc.2011.05.050. Epub 2011 May 30.
8
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