Suppr超能文献

格尔德霉素-阿魏酸缀合物作为一种有效的热休克蛋白90（Hsp90）抑制剂的合成及生物学评价

Synthesis and biological evaluation of geldanamycin-ferulic acid conjugate as a potent Hsp90 inhibitor.

作者信息

Li Zhenyu, Jia Lejiao, Tang Hui, Shen Yuemao, Shen Chengwu

机构信息

Department of Pharmacy, Shandong Provincial Hospital Affiliated to Shandong University Jinan 250021 Shandong P. R. China

Department of Pharmacy, Shandong University Qilu Hospital No. 107 West Wenhua Road Jinan 250012 Shandong P. R. China.

出版信息

RSC Adv. 2019 Dec 23;9(72):42509-42515. doi: 10.1039/c9ra08665j. eCollection 2019 Dec 18.

DOI:10.1039/c9ra08665j
PMID:35542888
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9076653/
Abstract

A novel geldanamycin-ferulic acid conjugate LZY228 was prepared and evaluated for anti-proliferation activity on human cancer cell line MDA-MB-231. Compound LZY228 exhibited potent cytotoxicity with IC value of 0.27 μM, which was more potent than 17-AAG. Hepatotoxicity test in mice demonstrated that the levels of both AST and ALT of LZY228-treated group were lower than that of GA-treated group, indicating that LZY228 was a promising antitumor candidate. In addition, excellent antitumor potency of LZY228 was observed in MDA-MB-231 xenograft model, which was superior to reference drug 17-AAG. Docking and MD refinement of the Hsp90-LZY228 complex give us an explanation of theoretical binding model of 17-ferulamido-17-demethoxygeldanamycins at molecular level.

摘要

制备了一种新型格尔德霉素-阿魏酸共轭物LZY228，并对其在人癌细胞系MDA-MB-231上的抗增殖活性进行了评估。化合物LZY228表现出强大的细胞毒性，IC值为0.27μM，比17-AAG更具活性。小鼠肝毒性试验表明，LZY228治疗组的AST和ALT水平均低于GA治疗组，表明LZY228是一种有前景的抗肿瘤候选物。此外，在MDA-MB-231异种移植模型中观察到LZY228具有优异的抗肿瘤效力，优于参考药物17-AAG。Hsp90-LZY228复合物的对接和分子动力学精修从分子水平上解释了17-阿魏酰胺-17-去甲氧基格尔德霉素的理论结合模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/563d/9076653/741fe5220023/c9ra08665j-f1.jpg

相似文献

1
Synthesis and biological evaluation of geldanamycin-ferulic acid conjugate as a potent Hsp90 inhibitor.
RSC Adv. 2019 Dec 23;9(72):42509-42515. doi: 10.1039/c9ra08665j. eCollection 2019 Dec 18.
2
In vitro and in vivo Evaluation of 17-phenylpropylamine/phenoxyethylamine- 17-demethoxygeldanamycins as Potent Hsp90 Inhibitors.
Med Chem. 2015;11(5):482-8. doi: 10.2174/1573406411666141230104953.
3
LZY3016, a novel geldanamycin derivative, inhibits tumor growth in an MDA-MB-231 xenograft model.
RSC Adv. 2023 May 3;13(20):13586-13591. doi: 10.1039/d3ra02131a. eCollection 2023 May 2.
4
Discovery of diamine-linked 17-aroylamido-17-demethoxygeldanamycins as potent Hsp90 inhibitors.
Eur J Med Chem. 2014 Nov 24;87:346-63. doi: 10.1016/j.ejmech.2014.09.078. Epub 2014 Sep 28.
5
Design, synthesis and biological evaluation of 17-arylmethylamine-17-demethoxygeldanamycin derivatives as potent Hsp90 inhibitors.
Eur J Med Chem. 2014 Oct 6;85:359-70. doi: 10.1016/j.ejmech.2014.07.101. Epub 2014 Aug 1.
6
Discovery of novel 17-phenylethylaminegeldanamycin derivatives as potent Hsp90 inhibitors.
Chem Biol Drug Des. 2015 Feb;85(2):181-8. doi: 10.1111/cbdd.12371. Epub 2014 Jun 26.
7
Synthesis and biological evaluation of geldanamycin analogs against human cancer cells.
Cancer Chemother Pharmacol. 2015 Apr;75(4):773-82. doi: 10.1007/s00280-015-2696-9. Epub 2015 Feb 14.
8
Non-benzoquinone geldanamycin analogs trigger various forms of death in human breast cancer cells.
J Exp Clin Cancer Res. 2016 Sep 22;35(1):149. doi: 10.1186/s13046-016-0428-6.
9
Small molecule inhibitor screening identifified HSP90 inhibitor 17-AAG as potential therapeutic agent for gallbladder cancer.
Oncotarget. 2017 Apr 18;8(16):26169-26184. doi: 10.18632/oncotarget.15410.
10
SNX-25a, a novel Hsp90 inhibitor, inhibited human cancer growth more potently than 17-AAG.
Biochem Biophys Res Commun. 2014 Jul 18;450(1):73-80. doi: 10.1016/j.bbrc.2014.05.076. Epub 2014 May 28.

引用本文的文献

1
Development of the first geldanamycin-based HSP90 degraders.
Front Chem. 2023 Jun 28;11:1219883. doi: 10.3389/fchem.2023.1219883. eCollection 2023.
2
LZY3016, a novel geldanamycin derivative, inhibits tumor growth in an MDA-MB-231 xenograft model.
RSC Adv. 2023 May 3;13(20):13586-13591. doi: 10.1039/d3ra02131a. eCollection 2023 May 2.
3
Targeting HIF-1α by Natural and Synthetic Compounds: A Promising Approach for Anti-Cancer Therapeutics Development.
Molecules. 2022 Aug 15;27(16):5192. doi: 10.3390/molecules27165192.
4
Paeonol promotes Opa1-mediated mitochondrial fusion via activating the CK2α-Stat3 pathway in diabetic cardiomyopathy.
Redox Biol. 2021 Oct;46:102098. doi: 10.1016/j.redox.2021.102098. Epub 2021 Aug 10.

本文引用的文献

1
Routine Microsecond Molecular Dynamics Simulations with AMBER on GPUs. 2. Explicit Solvent Particle Mesh Ewald.
J Chem Theory Comput. 2013 Sep 10;9(9):3878-88. doi: 10.1021/ct400314y. Epub 2013 Aug 20.
2
In vitro and in vivo Evaluation of 17-phenylpropylamine/phenoxyethylamine- 17-demethoxygeldanamycins as Potent Hsp90 Inhibitors.
Med Chem. 2015;11(5):482-8. doi: 10.2174/1573406411666141230104953.
3
Discovery of diamine-linked 17-aroylamido-17-demethoxygeldanamycins as potent Hsp90 inhibitors.
Eur J Med Chem. 2014 Nov 24;87:346-63. doi: 10.1016/j.ejmech.2014.09.078. Epub 2014 Sep 28.
4
Design, synthesis and biological evaluation of 17-arylmethylamine-17-demethoxygeldanamycin derivatives as potent Hsp90 inhibitors.
Eur J Med Chem. 2014 Oct 6;85:359-70. doi: 10.1016/j.ejmech.2014.07.101. Epub 2014 Aug 1.
5
Discovery of novel 17-phenylethylaminegeldanamycin derivatives as potent Hsp90 inhibitors.
Chem Biol Drug Des. 2015 Feb;85(2):181-8. doi: 10.1111/cbdd.12371. Epub 2014 Jun 26.
6
Synthesis of 19-substituted geldanamycins with altered conformations and their binding to heat shock protein Hsp90.
Nat Chem. 2013 Apr;5(4):307-14. doi: 10.1038/nchem.1596. Epub 2013 Mar 10.
7
Ferulic acid modulates fluoride-induced oxidative hepatotoxicity in male Wistar rats.
Biol Trace Elem Res. 2013 Jan;151(1):85-91. doi: 10.1007/s12011-012-9534-2. Epub 2012 Nov 14.
8
Routine Access to Millisecond Time Scale Events with Accelerated Molecular Dynamics.
J Chem Theory Comput. 2012 Sep 11;8(9):2997-3002. doi: 10.1021/ct300284c. Epub 2012 Jul 27.
9
Fluorine- and rhenium-containing geldanamycin derivatives as leads for the development of molecular probes for imaging Hsp90.
Org Biomol Chem. 2012 Sep 7;10(33):6724-31. doi: 10.1039/c2ob25744k. Epub 2012 Jul 24.
10
Routine Microsecond Molecular Dynamics Simulations with AMBER on GPUs. 1. Generalized Born.
J Chem Theory Comput. 2012 May 8;8(5):1542-1555. doi: 10.1021/ct200909j. Epub 2012 Mar 26.

文献AI研究员

20分钟写一篇综述，助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型，支持多种主流文档格式。

立即体验