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本文引用的文献

1
Lysophosphatidylinositols, from Cell Membrane Constituents to GPR55 Ligands.溶血磷脂酰肌醇，从细胞膜成分到 GPR55 配体。
Trends Pharmacol Sci. 2018 Jun;39(6):586-604. doi: 10.1016/j.tips.2018.02.011. Epub 2018 Mar 24.
2
Cancer statistics, 2018.癌症统计数据，2018 年。
CA Cancer J Clin. 2018 Jan;68(1):7-30. doi: 10.3322/caac.21442. Epub 2018 Jan 4.
3
Naphthoquinone Metabolites Produced by Monacrosporium ambrosium, the Ectosymbiotic Fungus of Tea Shot-Hole Borer, Euwallacea fornicatus, in Stems of Tea, Camellia sinensis.茶树茎干中茶材小蠹（Euwallacea fornicatus）的外共生真菌——安布罗斯单顶孢（Monacrosporium ambrosium）产生的萘醌代谢产物
J Chem Ecol. 2018 Jan;44(1):95-101. doi: 10.1007/s10886-017-0913-1. Epub 2018 Jan 2.
4
Triple negative breast cancer: Emerging therapeutic modalities and novel combination therapies.三阴性乳腺癌：新兴的治疗方式和新型联合疗法。
Cancer Treat Rev. 2018 Jan;62:110-122. doi: 10.1016/j.ctrv.2017.11.003. Epub 2017 Nov 13.
5
The LPI/GPR55 axis enhances human breast cancer cell migration via HBXIP and p-MLC signaling.LPI/GPR55 轴通过 HBXIP 和 p-MLC 信号促进人乳腺癌细胞迁移。
Acta Pharmacol Sin. 2018 Mar;39(3):459-471. doi: 10.1038/aps.2017.157. Epub 2017 Nov 30.
6
Quercetin/oleic acid-based G-protein-coupled receptor 40 ligands as new insulin secretion modulators.基于槲皮素/油酸的 G 蛋白偶联受体 40 配体作为新型胰岛素分泌调节剂。
Future Med Chem. 2017 Oct;9(16):1873-1885. doi: 10.4155/fmc-2017-0113. Epub 2017 Oct 24.
7
Aromatase inhibitory activity of 1,4-naphthoquinone derivatives and QSAR study.1,4-萘醌衍生物的芳香酶抑制活性及定量构效关系研究
EXCLI J. 2017 May 16;16:714-726. doi: 10.17179/excli2017-309. eCollection 2017.
8
Triple negative breast cancer: the kiss of death.三阴性乳腺癌：死亡之吻。
Oncotarget. 2017 Jul 11;8(28):46652-46662. doi: 10.18632/oncotarget.16938.
9
Peptide-guided targeting of GPR55 for anti-cancer therapy.用于抗癌治疗的肽引导性靶向GPR55
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10
New family of antimicrobial agents derived from 1,4-naphthoquinone.新型 1,4-萘醌类抗菌药物。
Eur J Med Chem. 2016 Nov 29;124:1019-1025. doi: 10.1016/j.ejmech.2016.10.034. Epub 2016 Oct 17.

发现1,4-萘醌作为一类靶向GPR55的新型抗增殖剂。

Discovery of 1,4-Naphthoquinones as a New Class of Antiproliferative Agents Targeting GPR55.

作者信息

Badolato Mariateresa, Carullo Gabriele, Caroleo Maria Cristina, Cione Erika, Aiello Francesca, Manetti Fabrizio

机构信息

Department of Pharmacy, Health and Nutritional Sciences - Department of Excellence 2018-2022, University of Calabria, Ed. Polifunzionale, 87036 Arcavacata di Rende (CS), Italy.

Department of Biotechnology, Chemistry and Pharmacy - Department of Excellence 2018-2022, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy.

出版信息

ACS Med Chem Lett. 2019 Feb 15;10(4):402-406. doi: 10.1021/acsmedchemlett.8b00333. eCollection 2019 Apr 11.

DOI:10.1021/acsmedchemlett.8b00333
PMID:30996770
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6466525/
Abstract

A new series of 1,4-naphthoquinones, bearing various cyclic and aliphatic amines on C2, was designed and synthesized to identify antiproliferative agents for triple-negative breast cancer, which represents a clinical challenge without targeted therapies. Among naphthoquinones, and inhibited the proliferation of MDA-MB-231 cells (EC = 1.6 and 2.7 μM, respectively), compared to primary human breast cells MCF10A. Furthermore, they did not affect the viability of peripheral blood mononuclear cells (PBMC), suggesting their potential safer use for cancer treatment. Recently, correlations have emerged between the expression of G protein-coupled receptor 55 (GPR55) and both triple-negative breast cancer development and invasion, making it a promising target for the development of targeted therapies. Based on this evidence, molecular docking studies supported the hypothesis of binding to GPR55, and pharmacological tests suggested that compound could exert its antiproliferative activity acting as a GPR55 inverse agonist.

摘要

设计并合成了一系列新的1,4-萘醌，其C2位带有各种环状和脂肪族胺，以鉴定三阴性乳腺癌的抗增殖剂，三阴性乳腺癌是一种缺乏靶向治疗的临床挑战。在萘醌中，与原代人乳腺细胞MCF10A相比，[具体化合物]和[具体化合物]抑制了MDA-MB-231细胞的增殖（EC50分别为1.6和2.7 μM）。此外，它们不影响外周血单核细胞（PBMC）的活力，表明它们在癌症治疗中可能更安全。最近，G蛋白偶联受体55（GPR55）的表达与三阴性乳腺癌的发展和侵袭之间出现了相关性，使其成为开发靶向治疗的一个有前景的靶点。基于这一证据，分子对接研究支持了与GPR55结合的假设，药理试验表明化合物[具体化合物]可作为GPR55反向激动剂发挥其抗增殖活性。