1-苯基-1-(喹唑啉-4-基)乙醇作为抗癌剂的合成及构效关系研究
Synthesis and Structure-Activity Relationship Study of 1-Phenyl-1-(quinazolin-4-yl)ethanols as Anticancer Agents.
作者信息
Kuroiwa Kenta, Ishii Hirosuke, Matsuno Kenji, Asai Akira, Suzuki Yumiko
机构信息
Department of Material and Life Sciences, Faculty of Science and Technology, Sophia University , 7-1 Kioicho, Chiyoda-ku, Tokyo 102-8554, Japan.
Graduate School of Pharmaceutical Sciences, University of Shizuoka , 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
出版信息
ACS Med Chem Lett. 2015 Jan 10;6(3):287-91. doi: 10.1021/ml5004684. eCollection 2015 Mar 12.
Abstract
A quinazoline derivative PVHD121 (1a) was shown to have strong antiproliferative activity against various tumor-derived cell lines, including A549 (lung), NCI-H460 (lung), HCT116 (colon), MCF7 (breast), PC3 (prostate), and HeLa (cervical) cells with IC50 values from 0.1 to 0.3 μM. A structure-activity relationship (SAR) study at the 2- and 4-position of the quinazoline core lead to the discovery of more potent anticancer agents (14, 16, 17, 19, 24, and 31). The results of an in vitro tubulin polymerization assay and fluorescent-based colchicine site competition assay with purified tubulin indicated that 1a inhibits tubulin polymerization by binding to the colchicine site.
摘要
喹唑啉衍生物PVHD121（1a）对多种肿瘤来源的细胞系具有很强的抗增殖活性，包括A549（肺癌）、NCI-H460（肺癌）、HCT116（结肠癌）、MCF7（乳腺癌）、PC3（前列腺癌）和HeLa（宫颈癌）细胞，IC50值为0.1至0.3μM。对喹唑啉核心2位和4位的构效关系（SAR）研究导致发现了更有效的抗癌剂（14、16、17、19、24和31）。用纯化微管蛋白进行的体外微管蛋白聚合测定和基于荧光的秋水仙碱位点竞争测定结果表明，1a通过与秋水仙碱位点结合来抑制微管蛋白聚合。
相似文献
1
Synthesis and Structure-Activity Relationship Study of 1-Phenyl-1-(quinazolin-4-yl)ethanols as Anticancer Agents.1-苯基-1-(喹唑啉-4-基)乙醇作为抗癌剂的合成及构效关系研究
ACS Med Chem Lett. 2015 Jan 10;6(3):287-91. doi: 10.1021/ml5004684. eCollection 2015 Mar 12.
2
Selective Inhibition of Spindle Microtubules by a Tubulin-Binding Quinazoline Derivative.微管结合的喹唑啉衍生物对纺锤体微管的选择性抑制。
Mol Pharmacol. 2019 Nov;96(5):609-618. doi: 10.1124/mol.119.116624. Epub 2019 Aug 30.
3
Synthesis and biological evaluation of curcumin inspired imidazo[1,2-a]pyridine analogues as tubulin polymerization inhibitors.姜黄素激发的咪唑并[1,2-a]吡啶类似物作为微管蛋白聚合抑制剂的合成及生物学评价
Eur J Med Chem. 2018 Jan 1;143:216-231. doi: 10.1016/j.ejmech.2017.11.010. Epub 2017 Nov 5.
4
Synthesis and biological evaluation of novel benzo[c]acridine-diones as potential anticancer agents and tubulin polymerization inhibitors.新型苯并[c]吖啶二酮类化合物的合成及生物评价作为潜在的抗癌药物和微管蛋白聚合抑制剂。
Arch Pharm (Weinheim). 2019 Jun;352(6):e1800307. doi: 10.1002/ardp.201800307. Epub 2019 Apr 23.
5
Synthesis of different heterocycles-linked chalcone conjugates as cytotoxic agents and tubulin polymerization inhibitors.合成不同杂环连接的查尔酮共轭物作为细胞毒性剂和微管蛋白聚合抑制剂。
Bioorg Med Chem. 2017 Sep 1;25(17):4805-4816. doi: 10.1016/j.bmc.2017.07.031. Epub 2017 Jul 21.
6
Design and synthesis of (2-(phenylamino)thieno[3,2-d]pyrimidin-4-yl)(3,4,5-trimethoxyphenyl)methanone analogues as potent anti-tubulin polymerization agents.（2-（苯氨基）噻吩[3,2-d]嘧啶-4-基）（3,4,5-三甲氧基苯基）甲酮类似物的设计与合成及其作为有效的微管聚合抑制剂。
Eur J Med Chem. 2019 Dec 1;183:111679. doi: 10.1016/j.ejmech.2019.111679. Epub 2019 Sep 5.
7
The discovery of novel indazole derivatives as tubulin colchicine site binding agents that displayed potent antitumor activity both in vitro and in vivo.发现新型吲唑衍生物作为微管蛋白秋水仙碱结合剂，在体外和体内均显示出强大的抗肿瘤活性。
Eur J Med Chem. 2020 Feb 1;187:111968. doi: 10.1016/j.ejmech.2019.111968. Epub 2019 Dec 14.
8
2-Alkoxycarbonyl-3-arylamino-5-substituted thiophenes as a novel class of antimicrotubule agents: Design, synthesis, cell growth and tubulin polymerization inhibition.2-烷氧羰基-3-芳氨基-5-取代噻吩类新型抗微管蛋白剂：设计、合成、细胞生长及微管蛋白聚合抑制作用
Eur J Med Chem. 2018 Jan 1;143:683-698. doi: 10.1016/j.ejmech.2017.11.096.
9
2,3-Dihydroquinazolin-4(1)-ones and quinazolin-4(3)-ones as broad-spectrum cytotoxic agents and their impact on tubulin polymerisation.2,3-二氢喹唑啉-4(1)-酮和喹唑啉-4(3)-酮作为广谱细胞毒性剂及其对微管蛋白聚合的影响。
RSC Med Chem. 2024 Mar 6;15(5):1686-1708. doi: 10.1039/d3md00600j. eCollection 2024 May 22.
10
Synthesis, biological evaluation and molecular docking studies of aminochalcone derivatives as potential anticancer agents by targeting tubulin colchicine binding site.以微管蛋白秋水仙碱结合位点为靶点的氨基查尔酮衍生物的合成、生物评价及分子对接研究。
Bioorg Chem. 2018 Aug;78:332-340. doi: 10.1016/j.bioorg.2018.03.028. Epub 2018 Apr 3.
引用本文的文献
1
Inducible mismatch repair streamlines forward genetic approaches to target identification of cytotoxic small molecules.诱导错配修复简化了靶向鉴定细胞毒性小分子的正向遗传学方法。
Cell Chem Biol. 2023 Nov 16;30(11):1453-1467.e8. doi: 10.1016/j.chembiol.2023.07.017. Epub 2023 Aug 21.
2
Cobalt-electrocatalytic C-H hydroxyalkylation of -heteroarenes with trifluoromethyl ketones.钴催化杂芳烃与三氟甲基酮的C-H羟基烷基化反应
Chem Sci. 2022 Nov 21;14(1):143-148. doi: 10.1039/d2sc05198b. eCollection 2022 Dec 21.
3
Discovery of a Potent Anticancer Agent PVHD303 with Activity.具有活性的强效抗癌剂PVHD303的发现。
ACS Med Chem Lett. 2020 May 8;11(6):1287-1291. doi: 10.1021/acsmedchemlett.0c00119. eCollection 2020 Jun 11.
4
An insight into the therapeutic potential of quinazoline derivatives as anticancer agents.喹唑啉衍生物作为抗癌剂的治疗潜力洞察。
Medchemcomm. 2017 Apr 7;8(5):871-885. doi: 10.1039/c7md00097a. eCollection 2017 May 1.
本文引用的文献
1
Optimization of 4-(N-cycloamino)phenylquinazolines as a novel class of tubulin-polymerization inhibitors targeting the colchicine site.优化 4-(N-环氨基)苯基喹唑啉类化合物作为靶向秋水仙碱结合部位的新型微管蛋白聚合抑制剂。
J Med Chem. 2014 Feb 27;57(4):1390-402. doi: 10.1021/jm4016526. Epub 2014 Feb 6.
2
Toward highly potent cancer agents by modulating the C-2 group of the arylthioindole class of tubulin polymerization inhibitors.通过调节芳基硫代吲哚类微管聚合抑制剂的 C-2 基团来开发高效的癌症治疗剂。
J Med Chem. 2013 Jan 10;56(1):123-49. doi: 10.1021/jm3013097. Epub 2012 Dec 27.
3
Quinazoline derivatives as potential anticancer agents: a patent review (2007 - 2010).喹唑啉衍生物作为潜在的抗癌剂：专利审查（2007-2010）。
Expert Opin Ther Pat. 2012 Mar;22(3):223-52. doi: 10.1517/13543776.2012.665876. Epub 2012 Mar 12.
4
Structure-activity relationships of ustiloxin analogues.稻曲毒素类似物的构效关系。
Tetrahedron Lett. 2011 Apr;52(17):2136-2139. doi: 10.1016/j.tetlet.2010.11.165.
5
Discovery of N-(4-methoxyphenyl)-N,2-dimethylquinazolin-4-amine, a potent apoptosis inducer and efficacious anticancer agent with high blood brain barrier penetration.N-(4-甲氧基苯基)-N,2-二甲基喹唑啉-4-胺的发现，一种强效的凋亡诱导剂和具有高血脑屏障穿透性的有效抗癌剂。
J Med Chem. 2009 Apr 23;52(8):2341-51. doi: 10.1021/jm801315b.
6
Discovery of quinazolines as histamine H4 receptor inverse agonists using a scaffold hopping approach.采用骨架跃迁方法发现喹唑啉类化合物作为组胺H4受体反向激动剂
J Med Chem. 2008 Dec 25;51(24):7855-65. doi: 10.1021/jm800876b.
7
A history of cancer chemotherapy.癌症化疗史。
Cancer Res. 2008 Nov 1;68(21):8643-53. doi: 10.1158/0008-5472.CAN-07-6611.
8
Microtubule-associated proteins as targets in cancer chemotherapy.微管相关蛋白作为癌症化疗的靶点
Clin Cancer Res. 2007 May 15;13(10):2849-54. doi: 10.1158/1078-0432.CCR-06-3040.
9
Synthesis and biological evaluation of 2-(3',4',5'-trimethoxybenzoyl)-3-amino 5-aryl thiophenes as a new class of tubulin inhibitors.新型微管蛋白抑制剂2-(3',4',5'-三甲氧基苯甲酰基)-3-氨基-5-芳基噻吩的合成与生物学评价
J Med Chem. 2006 Oct 19;49(21):6425-8. doi: 10.1021/jm060804a.
10
Understanding microtubule dynamics for improved cancer therapy.了解微管动力学以改进癌症治疗。
Cell Mol Life Sci. 2005 Dec;62(24):3039-56. doi: 10.1007/s00018-005-5330-x.
Zotero 插件