环-C 修饰的秋水仙碱类似物的合成与生物评价。
Syntheses and biological evaluation of ring-C modified colchicine analogs.
机构信息
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA.
出版信息
Bioorg Med Chem Lett. 2010 Jun 15;20(12):3831-3. doi: 10.1016/j.bmcl.2010.03.056. Epub 2010 Mar 15.
Abstract
Ring-C modified alkaloids were synthesized from colchicine using iminonitroso Diels-Alder reactions in a highly regio- and stereoselective fashion. Several analogs exhibited cytotoxic activity similar to that of colchicine itself against PC-3 and MCF-7 cancer cell lines, by serving as prodrugs of colchicine through retro Diels-Alder reactions under the assayed conditions. In vitro microtubule polymerization assays indicated that these modifications affected their interaction with tubulin.
摘要
环-C 修饰的生物碱是通过亚胺硝酮 Diels-Alder 反应从秋水仙碱合成的，具有高度的区域和立体选择性。几种类似物表现出与秋水仙碱本身相似的细胞毒性活性，作为秋水仙碱的前药，通过在测定条件下的反 Diels-Alder 反应。体外微管聚合试验表明，这些修饰影响了它们与微管蛋白的相互作用。
相似文献
1
Syntheses and biological evaluation of ring-C modified colchicine analogs.环-C 修饰的秋水仙碱类似物的合成与生物评价。
Bioorg Med Chem Lett. 2010 Jun 15;20(12):3831-3. doi: 10.1016/j.bmcl.2010.03.056. Epub 2010 Mar 15.
2
Synthesis and biological evaluation of B-ring modified colchicine and isocolchicine analogs.B 环修饰的秋水仙碱和异秋水仙碱类似物的合成及生物学评价
Bioorg Med Chem Lett. 2006 May 15;16(10):2761-4. doi: 10.1016/j.bmcl.2006.02.010. Epub 2006 Feb 28.
3
Antitumor agents. Part 215: antitubulin effects of cytotoxic B-ring modified allocolchicinoids.
Bioorg Med Chem Lett. 2002 Oct 21;12(20):2851-3. doi: 10.1016/s0960-894x(02)00635-2.
4
Caulerpenyne-colchicine hybrid: synthesis and biological evaluation.刺参炔苷 - 秋水仙碱杂合物：合成与生物学评价
Bioorg Med Chem. 2006 Aug 15;14(16):5540-8. doi: 10.1016/j.bmc.2006.04.024. Epub 2006 May 22.
5
Synthesis and structure-activity relationship of boronic acid bioisosteres of combretastatin A-4 as anticancer agents.作为抗癌剂的康普瑞他汀A-4硼酸生物电子等排体的合成及构效关系
Bioorg Med Chem. 2024 Dec 15;116:117999. doi: 10.1016/j.bmc.2024.117999. Epub 2024 Nov 10.
6
New Combretastatin Analogs as Anticancer Agents: Design, Synthesis, Microtubules Polymerization Inhibition, and Molecular Docking Studies.新型康普瑞汀类似物作为抗癌剂：设计、合成、微管聚合抑制及分子对接研究。
Chem Biodivers. 2023 Apr;20(4):e202201206. doi: 10.1002/cbdv.202201206. Epub 2023 Mar 8.
7
Potent colchicine-site ligands with improved intrinsic solubility by replacement of the 3,4,5-trimethoxyphenyl ring with a 2-methylsulfanyl-6-methoxypyridine ring.用 2-甲硫基-6-甲氧基吡啶环取代 3,4,5-三甲氧基苯基环，得到具有改善的内在溶解度的强效秋水仙碱结合位点配体。
Bioorg Chem. 2020 May;98:103755. doi: 10.1016/j.bioorg.2020.103755. Epub 2020 Mar 13.
8
Antitumor agents. Part 236: Synthesis of water-soluble colchicine derivatives.抗肿瘤剂。第236部分：水溶性秋水仙碱衍生物的合成。
Bioorg Med Chem Lett. 2005 Jan 3;15(1):235-8. doi: 10.1016/j.bmcl.2004.07.098.
9
Synthesis, antiproliferative activity and molecular docking of thiocolchicine urethanes.硫代秋水仙碱尿烷的合成、抗增殖活性及分子对接。
Bioorg Chem. 2018 Dec;81:553-566. doi: 10.1016/j.bioorg.2018.09.004. Epub 2018 Sep 12.
10
Novel B-ring modified allocolchicinoids of the NCME series: design, synthesis, antimicrotubule activity and cytotoxicity.新型NCME系列B环修饰的别秋水仙碱类化合物：设计、合成、抗微管活性及细胞毒性
Bioorg Med Chem. 2003 Apr 3;11(7):1269-81. doi: 10.1016/s0968-0896(02)00639-9.
引用本文的文献
1
Colchicine-like β-acetamidoketones as inhibitors of microtubule polymerization: Design, synthesis and biological evaluation of anticancer activity.类秋水仙碱β-乙酰氨基酮作为微管聚合抑制剂：抗癌活性的设计、合成及生物学评价
Iran J Basic Med Sci. 2019 Oct;22(10):1138-1146. doi: 10.22038/ijbms.2019.34760.8242.
2
Stereo- and regioselectivity of the hetero-Diels-Alder reaction of nitroso derivatives with conjugated dienes.亚硝基衍生物与共轭二烯的杂环狄尔斯-阿尔德反应的立体选择性和区域选择性。
Beilstein J Org Chem. 2016 Sep 1;12:1949-1980. doi: 10.3762/bjoc.12.184. eCollection 2016.
3
Nitroso Diels-Alder (NDA) reaction as an efficient tool for the functionalization of diene-containing natural products.亚硝基狄尔斯-阿尔德（NDA）反应作为一种用于含二烯天然产物功能化的有效工具。
Org Biomol Chem. 2014 Oct 14;12(38):7445-68. doi: 10.1039/c4ob01033g.
4
Reviewing Colchicaceae alkaloids - perspectives of evolution on medicinal chemistry.秋水仙科生物碱综述——药物化学的进化视角
Curr Top Med Chem. 2014;14(2):274-89. doi: 10.2174/1568026613666131216110417.
本文引用的文献
1
Retro iminonitroso Diels-Alder reactions: interconversion of nitroso cycloadducts.反式亚胺基亚硝基Diels-Alder反应：亚硝基环加成产物的相互转化
Tetrahedron Lett. 2009 Oct 1;50(43):5879-5883. doi: 10.1016/j.tetlet.2009.07.121.
2
Iminonitroso Diels-Alder reactions for efficient derivatization and functionalization of complex diene-containing natural products.用于复杂含二烯天然产物高效衍生化和功能化的亚胺基亚硝基Diels-Alder反应
Org Lett. 2007 Jul 19;9(15):2923-6. doi: 10.1021/ol071322b. Epub 2007 Jun 30.
3
Anti-mitotic activity of colchicine and the structural basis for its interaction with tubulin.秋水仙碱的抗有丝分裂活性及其与微管蛋白相互作用的结构基础。
Med Res Rev. 2008 Jan;28(1):155-83. doi: 10.1002/med.20097.
4
Insight into tubulin regulation from a complex with colchicine and a stathmin-like domain.从与秋水仙碱和类微管相关蛋白结构域的复合物中洞察微管蛋白调控机制。
Nature. 2004 Mar 11;428(6979):198-202. doi: 10.1038/nature02393.
5
Novel antitumor agents from higher plants.
Med Res Rev. 1999 Nov;19(6):569-96. doi: 10.1002/(sici)1098-1128(199911)19:6<569::aid-med7>3.0.co;2-9.
6
Mechanism of tubulin-colchicine recognition: a kinetic study of the binding of the colchicine analogues colchicide and isocolchicine.微管蛋白-秋水仙碱识别机制：秋水仙碱类似物秋水仙酰胺和异秋水仙碱结合的动力学研究
Biochem J. 1997 Nov 1;327 ( Pt 3)(Pt 3):685-8. doi: 10.1042/bj3270685.
7
Toxicity quantitative structure--activity relationships of colchicines.秋水仙碱的毒性定量构效关系
J Med Chem. 1981 May;24(5):636-9. doi: 10.1021/jm00137a031.
8
The binding of isocolchicine to tubulin. Mechanisms of ligand association with tubulin.
J Biol Chem. 1989 Apr 25;264(12):6682-8.
Zotero 插件