Anti-tuberculosis activity and structure-activity relationships of oxygenated tricyclic carbazole alkaloids and synthetic derivatives

被引：37

作者：

Boerger, Carsten ^{[1
]}

Bruetting, Christian ^{[1
]}

Julich-Gruner, Konstanze K. ^{[1
]}

Hesse, Ronny ^{[1
]}

Kumar, V. Pavan ^{[1
]}

Kutz, Sebastian K. ^{[1
]}

Roennefahrt, Marika ^{[1
]}

Thomas, Claudia ^{[1
]}

Wan, Baojie ^{[2
]}

Franzblau, Scott G. ^{[2
]}

Knoelker, Hans-Joachim ^{[1
]}

机构：

[1] Tech Univ Dresden, Dept Chem, Bergstr 66, D-01069 Dresden, Germany

[2] Univ Illinois, Inst TB Res, Coll Pharm, 833 S Wood St,MC 964, Chicago, IL 60612 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2017年 / 25卷 / 22期

关键词：

Alkaloids; Anti-TB activity; Carbazoles; Natural products; Tuberculosis; TRANSITION-METAL-COMPLEXES; 1ST TOTAL-SYNTHESIS; CATALYZED TOTAL-SYNTHESIS; MEDIATED TOTAL-SYNTHESIS; ORGANIC-SYNTHESIS; OXIDATIVE CYCLIZATION; NATURAL-PRODUCTS; CLAUSINE-L; MUKONIDINE; INDOLOQUINONES;

D O I：

10.1016/j.bmc.2016.12.038

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A series of 49 oxygenated tricyclic carbazole derivatives has been tested for inhibition of the growth of Mycobacterium tuberculosis and a mammalian cell line (vero cells). From this series, twelve carbazoles showed a significant anti-TB activity. The four most active compounds were the naturally occurring carbazole alkaloids clauszoline-M (45), murrayaline-C (41), carbalexin-C (27), and the synthetic carbazole derivative 22 with MIC90 values ranging from 1.5 to 3.7 mu M. The active compounds were virtually non-toxic for the mammalian cell line in the concentration range up to 50 mu M. (C) 2016 Elsevier Ltd. All rights reserved.

引用

页码：6167 / 6174

页数：8

共 56 条

[1]

[Anonymous], 2017, Global tuberculosis report

[2]

[Anonymous], 2013, ANGEW CHEM INT ED, V52, P11073

[3] anti-Tuberculosis natural products: synthesis and biological evaluation of pyridoacridine alkaloids related to ascididemin [J].

Appleton, David R. ;

Pearce, A. Norrie ;

Copp, Brent R. .

TETRAHEDRON, 2010, 66 (27-28) :4977-4986

[4] Synthesis of Pyrrole and Carbazole Alkaloids [J].

Bauer, Ingmar ;

Knoelker, Hans-Joachim .

ALKALOID SYNTHESIS, 2012, 309 :203-253

[5] Transition metals in organic synthesis, part 85.: A general approach to 1,6-dioxygenated carbazole alkaloids -: First total synthesis of clausine G, clausine I, and clausine Z [J].

Boerger, Carsten ;

Knoelker, Hans-Joachim .

SYNLETT, 2008, (11) :1698-1702

[6] Transition metals in organic synthesis. Part 101: Convergent total synthesis of 1,6-dioxygenated carbazole alkaloids [J].

Boerger, Carsten ;

Knoelker, Hans-Joachim .

TETRAHEDRON, 2012, 68 (33) :6727-6736

[7]

Chakraborty D P, 1991, Fortschr Chem Org Naturst, V57, P71

[8]

Chakraborty D.P., 1993, ALKALOIDS, V44, P257, DOI [10.1016/S0099-9598(08)60146-7, DOI 10.1016/S0099-9598(08)60146-7]

[9]

Cho Sanghyun, 2015, Methods Mol Biol, V1285, P281, DOI 10.1007/978-1-4939-2450-9_17

[10] Transition metals in organic synthesis -: Part 83#:: Synthesis and pharmacological potential of carbazoles [J].

Choi, Taylor A. ;

Czerwonka, Regina ;

Forke, Ronny ;

Jaeger, Anne ;

Knoell, Jan ;

Krahl, Micha P. ;

Krause, Tilo ;

Reddy, Kethiri R. ;

Franzblau, Scott G. ;

Knoelker, Hans-Joachim .

MEDICINAL CHEMISTRY RESEARCH, 2008, 17 (2-7) :374-385

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