一种新型普拉地诺内酯类似物支架的设计、合成及初步生物学评价
Design, synthesis and initial biological evaluation of a novel pladienolide analog scaffold.
作者信息
Gundluru Mahesh Kumar, Pourpak Alan, Cui Xiaoli, Morris Stephan W, Webb Thomas R
机构信息
Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105, U.S.A. ; Tel: 901 595 3928.
出版信息
Medchemcomm. 2011 Jan 1;2(9):904-908. doi: 10.1039/C1MD00040C.
Abstract
A novel and simplified synthetic scaffold based on pladienolide was designed using a consensus pharmacophore hypothesis. An initial target was synthesized and evaluated to examine the role of the 3-hydroxy group and the methyl groups present at positions 10, 16, 20, 22 in 1, on biological activity. We report the first totally synthetic analog of this macrolide that shows biological activity. Our novel synthetic strategy enables the rapid synthesis of other new analogs of pladienolide in order to develop selective anticancer lead compounds.
摘要
基于共药效团假说设计了一种新型的、简化的基于普拉地诺内酯的合成支架。合成并评估了一个初始靶点，以研究1中3-羟基以及10、16、20、22位甲基对生物活性的作用。我们报道了这种大环内酯的首个具有生物活性的全合成类似物。我们新颖的合成策略能够快速合成普拉地诺内酯的其他新类似物，以便开发选择性抗癌先导化合物。
相似文献
1
Design, synthesis and initial biological evaluation of a novel pladienolide analog scaffold.
Medchemcomm. 2011 Jan 1;2(9):904-908. doi: 10.1039/C1MD00040C.
2
Biological validation that SF3b is a target of the antitumor macrolide pladienolide.
FEBS J. 2011 Dec;278(24):4870-80. doi: 10.1111/j.1742-4658.2011.08387.x. Epub 2011 Oct 31.
3
Enantioselective synthesis of pladienolide B and truncated analogues as new anticancer agents.
Org Lett. 2013 Jul 19;15(14):3610-3. doi: 10.1021/ol401458d. Epub 2013 Jul 3.
4
Pharmacophore & QSAR Guided Design, Synthesis, Pharmacokinetics and Evaluation of Curcumin Analogs for Anticancer Activity.
Curr Med Chem. 2024;31(5):620-639. doi: 10.2174/0929867330666230428162720.
5
Pre-mRNA splicing-modulatory pharmacophores: the total synthesis of herboxidiene, a pladienolide-herboxidiene hybrid analog and related derivatives.
ACS Chem Biol. 2014 Mar 21;9(3):643-8. doi: 10.1021/cb400695j. Epub 2013 Dec 30.
6
Total Syntheses of Pladienolide-Derived Spliceosome Modulators.
Molecules. 2021 Sep 30;26(19):5938. doi: 10.3390/molecules26195938.
7
Antitumor compounds based on a natural product consensus pharmacophore.
J Med Chem. 2008 Oct 9;51(19):6220-4. doi: 10.1021/jm8006195. Epub 2008 Sep 13.
8
3D-QSAR pharmacophore modelling, virtual screening and docking studies for lead discovery of a novel scaffold for VEGFR 2 inhibitors: Design, synthesis and biological evaluation.
Bioorg Chem. 2019 Aug;89:102988. doi: 10.1016/j.bioorg.2019.102988. Epub 2019 May 18.
9
Coherence between cellular responses and in vitro splicing inhibition for the anti-tumor drug pladienolide B and its analogs.
J Biol Chem. 2014 Jan 24;289(4):1938-47. doi: 10.1074/jbc.M113.515536. Epub 2013 Dec 3.
10
High antitumor activity of pladienolide B and its derivative in gastric cancer.
Cancer Sci. 2014 Jan;105(1):110-6. doi: 10.1111/cas.12317. Epub 2013 Dec 4.
引用本文的文献
1
Total Syntheses of Pladienolide-Derived Spliceosome Modulators.
Molecules. 2021 Sep 30;26(19):5938. doi: 10.3390/molecules26195938.
2
Design and Synthesis of 1,2-Deoxy-pyranose Derivatives of Spliceostatin A toward Prostate Cancer Treatment.
ACS Med Chem Lett. 2020 May 1;11(6):1310-1315. doi: 10.1021/acsmedchemlett.0c00153. eCollection 2020 Jun 11.
3
A triple exon-skipping luciferase reporter assay identifies a new CLK inhibitor pharmacophore.
Bioorg Med Chem Lett. 2017 Feb 1;27(3):406-412. doi: 10.1016/j.bmcl.2016.12.056. Epub 2016 Dec 24.
4
Modulating splicing with small molecular inhibitors of the spliceosome.
Wiley Interdiscip Rev RNA. 2017 Mar;8(2). doi: 10.1002/wrna.1381. Epub 2016 Jul 21.
5
Interchangeable SF3B1 inhibitors interfere with pre-mRNA splicing at multiple stages.
RNA. 2016 Mar;22(3):350-9. doi: 10.1261/rna.053108.115. Epub 2016 Jan 7.
6
Pre-mRNA splicing-modulatory pharmacophores: the total synthesis of herboxidiene, a pladienolide-herboxidiene hybrid analog and related derivatives.
ACS Chem Biol. 2014 Mar 21;9(3):643-8. doi: 10.1021/cb400695j. Epub 2013 Dec 30.
7
Optimization of antitumor modulators of pre-mRNA splicing.
J Med Chem. 2013 Dec 27;56(24):10033-44. doi: 10.1021/jm401370h. Epub 2013 Dec 11.
8
Coherence between cellular responses and in vitro splicing inhibition for the anti-tumor drug pladienolide B and its analogs.
J Biol Chem. 2014 Jan 24;289(4):1938-47. doi: 10.1074/jbc.M113.515536. Epub 2013 Dec 3.
9
Stabilized cyclopropane analogs of the splicing inhibitor FD-895.
J Med Chem. 2013 Sep 12;56(17):6576-82. doi: 10.1021/jm400861t. Epub 2013 Aug 21.
10
Enantioselective total synthesis of pladienolide B: a potent spliceosome inhibitor.
Org Lett. 2012 Sep 21;14(18):4730-3. doi: 10.1021/ol301886g. Epub 2012 Sep 6.
本文引用的文献
1
Reduced fidelity of branch point recognition and alternative splicing induced by the anti-tumor drug spliceostatin A.
Genes Dev. 2011 Mar 1;25(5):445-59. doi: 10.1101/gad.2014311.
2
The anti-tumor drug E7107 reveals an essential role for SF3b in remodeling U2 snRNP to expose the branch point-binding region.
Genes Dev. 2011 Mar 1;25(5):440-4. doi: 10.1101/gad.2009411.
3
Sudemycins, novel small molecule analogues of FR901464, induce alternative gene splicing.
ACS Chem Biol. 2011 Jun 17;6(6):582-9. doi: 10.1021/cb100356k. Epub 2011 Mar 7.
4
Synthetic mRNA splicing modulator compounds with in vivo antitumor activity.
J Med Chem. 2009 Nov 26;52(22):6979-90. doi: 10.1021/jm901215m.
5
Antitumor compounds based on a natural product consensus pharmacophore.
J Med Chem. 2008 Oct 9;51(19):6220-4. doi: 10.1021/jm8006195. Epub 2008 Sep 13.
6
Synthesis of the macrocyclic core of (-)-pladienolide B.
Org Lett. 2008 Jul 3;10(13):2821-4. doi: 10.1021/ol800946x. Epub 2008 May 30.
7
Mosher ester analysis for the determination of absolute configuration of stereogenic (chiral) carbinol carbons.
Nat Protoc. 2007;2(10):2451-8. doi: 10.1038/nprot.2007.354.
8
A synthetic entry to pladienolide B and FD-895.
Bioorg Med Chem Lett. 2007 Sep 15;17(18):5159-64. doi: 10.1016/j.bmcl.2007.06.094. Epub 2007 Jul 7.
9
Splicing factor SF3b as a target of the antitumor natural product pladienolide.
Nat Chem Biol. 2007 Sep;3(9):570-5. doi: 10.1038/nchembio.2007.16. Epub 2007 Jul 22.
10
Spliceostatin A targets SF3b and inhibits both splicing and nuclear retention of pre-mRNA.
Nat Chem Biol. 2007 Sep;3(9):576-83. doi: 10.1038/nchembio.2007.18. Epub 2007 Jul 22.
Zotero 插件