2-芳氨基苯并噻唑-芳基丙烯酮缀合物作为微管蛋白聚合抑制剂
2-Arylaminobenzothiazole-arylpropenone conjugates as tubulin polymerization inhibitors.
作者信息
Subba Rao A V, Rao Bala Bhaskara, Sunkari Satish, Shaik Siddiq Pasha, Shaik Bajee, Kamal Ahmed
机构信息
Medicinal Chemistry and Pharmacology , India.
Academy of Scientific and Innovative Research (AcSIR) , India.
出版信息
Medchemcomm. 2017 Mar 7;8(5):924-941. doi: 10.1039/c6md00562d. eCollection 2017 May 1.
Abstract
A new series of 2-arylaminobenzothiazole-arylpropenone conjugates -(-) was designed, synthesized and investigated for their cytotoxic potency against the various human cancer cell lines. Most of these conjugates exhibited cytotoxic activity and inhibited tubulin polymerization effectively. Conjugates and cause cell cycle blocks in the G2/M phase in HeLa cells and treatments with and manifested increased mRNA and protein levels of the G2/M marker, cyclin B1. Immunocytochemistry revealed loss of intact microtubule structure in cells treated with and . Western blot analysis revealed that these conjugates accumulate more tubulin in the soluble fraction. Moreover, the triggering of apoptotic cell death after mitotic arrest was investigated by studying their effect on Hoechst staining, mitochondrial membrane potential, ROS generation.
摘要
设计、合成了一系列新的2-芳基氨基苯并噻唑-芳基丙烯酮共轭物-(-)，并研究了它们对各种人类癌细胞系的细胞毒性。这些共轭物大多表现出细胞毒性活性，并能有效抑制微管蛋白聚合。共轭物和导致HeLa细胞在G2/M期出现细胞周期阻滞，用和处理后，G2/M标记物细胞周期蛋白B1的mRNA和蛋白质水平升高。免疫细胞化学显示，用和处理的细胞中完整的微管结构丧失。蛋白质印迹分析显示，这些共轭物在可溶性部分积累了更多的微管蛋白。此外，通过研究它们对Hoechst染色、线粒体膜电位、活性氧生成的影响，研究了有丝分裂停滞后凋亡性细胞死亡的触发情况。
相似文献
1
2-Arylaminobenzothiazole-arylpropenone conjugates as tubulin polymerization inhibitors.2-芳氨基苯并噻唑-芳基丙烯酮缀合物作为微管蛋白聚合抑制剂
Medchemcomm. 2017 Mar 7;8(5):924-941. doi: 10.1039/c6md00562d. eCollection 2017 May 1.
2
Design and synthesis of 1,2,3-triazolo linked benzo[d]imidazo[2,1-b]thiazole conjugates as tubulin polymerization inhibitors.作为微管蛋白聚合抑制剂的1,2,3-三唑连接的苯并[d]咪唑并[2,1-b]噻唑共轭物的设计与合成
Bioorg Med Chem. 2017 Jul 1;25(13):3285-3297. doi: 10.1016/j.bmc.2017.04.013. Epub 2017 Apr 12.
3
Synthesis and biological evaluation of 1,2,3-triazole linked aminocombretastatin conjugates as mitochondrial mediated apoptosis inducers.1,2,3-三唑连接的氨基秋水仙碱缀合物作为线粒体介导的凋亡诱导剂的合成及生物学评价
Bioorg Med Chem. 2014 Oct 1;22(19):5155-67. doi: 10.1016/j.bmc.2014.08.008. Epub 2014 Aug 19.
4
Synthesis and biological evaluation of cis-restricted triazole/tetrazole mimics of combretastatin-benzothiazole hybrids as tubulin polymerization inhibitors and apoptosis inducers.作为微管蛋白聚合抑制剂和凋亡诱导剂的柯里拉京-苯并噻唑杂合物的顺式受限三唑/四唑模拟物的合成及生物学评价
Bioorg Med Chem. 2017 Feb 1;25(3):977-999. doi: 10.1016/j.bmc.2016.12.010. Epub 2016 Dec 9.
5
Synthesis of benzo[d]imidazo[2,1-b]thiazole-chalcone conjugates as microtubule targeting and apoptosis inducing agents.苯并[d]咪唑并[2,1-b]噻唑-查尔酮轭合物的合成及其作为微管靶向和诱导细胞凋亡的试剂。
Bioorg Chem. 2018 Feb;76:1-12. doi: 10.1016/j.bioorg.2017.10.019. Epub 2017 Nov 2.
6
Click chemistry-assisted synthesis of triazolo linked podophyllotoxin conjugates as tubulin polymerization inhibitors.点击化学辅助合成三唑连接的鬼臼毒素缀合物作为微管蛋白聚合抑制剂。
Medchemcomm. 2017 Jul 18;8(9):1817-1823. doi: 10.1039/c7md00273d. eCollection 2017 Sep 1.
7
Synthesis and biological evaluation of imidazo[1,5-a]pyridine-benzimidazole hybrids as inhibitors of both tubulin polymerization and PI3K/Akt pathway.咪唑并[1,5-a]吡啶-苯并咪唑杂化物作为微管蛋白聚合和PI3K/Akt途径抑制剂的合成及生物学评价
Org Biomol Chem. 2014 Dec 28;12(48):9864-80. doi: 10.1039/c4ob01930j.
8
Synthesis of a terphenyl substituted 4-aza-2,3-didehydropodophyllotoxin analogues as inhibitors of tubulin polymerization and apoptosis inducers.一种三联苯取代的4-氮杂-2,3-二脱氢鬼臼毒素类似物的合成及其作为微管蛋白聚合抑制剂和凋亡诱导剂的研究
Bioorg Med Chem. 2014 May 1;22(9):2714-23. doi: 10.1016/j.bmc.2014.03.021. Epub 2014 Mar 22.
9
Design and synthesis of imidazo[2,1-b]thiazole-chalcone conjugates: microtubule-destabilizing agents.咪唑并[2,1-b]噻唑-查耳酮共轭物的设计与合成：微管破坏剂
ChemMedChem. 2014 Dec;9(12):2766-80. doi: 10.1002/cmdc.201402310. Epub 2014 Oct 14.
10
Targeting of tubulin polymerization and induction of mitotic blockage by Methyl 2-(5-fluoro-2-hydroxyphenyl)-1H-benzo[d]imidazole-5-carboxylate (MBIC) in human cervical cancer HeLa cell.2-(5-氟-2-羟基苯基)-1H-苯并[d]咪唑-5-羧酸甲酯（MBIC）对人宫颈癌HeLa细胞中微管蛋白聚合的靶向作用及有丝分裂阻滞的诱导
J Exp Clin Cancer Res. 2016 Mar 31;35:58. doi: 10.1186/s13046-016-0332-0.
引用本文的文献
1
Design, synthesis, molecular docking and anticancer activity of benzothiazolecarbohydrazide-sulfonate conjugates: insights into ROS-induced DNA damage and tubulin polymerization inhibition.苯并噻唑碳酰肼 - 磺酸盐共轭物的设计、合成、分子对接及抗癌活性：对活性氧诱导的DNA损伤和微管蛋白聚合抑制的见解
RSC Adv. 2025 Feb 21;15(8):5895-5905. doi: 10.1039/d4ra07810a. eCollection 2025 Feb 19.
2
Synthetic Approaches to Biologically Active C-2-Substituted Benzothiazoles.C-2 取代苯并噻唑类生物活性化合物的合成方法。
Molecules. 2022 Apr 18;27(8):2598. doi: 10.3390/molecules27082598.
3
Benzothiazole derivatives as anticancer agents.苯并噻唑衍生物作为抗癌剂。
J Enzyme Inhib Med Chem. 2020 Dec;35(1):265-279. doi: 10.1080/14756366.2019.1698036.
本文引用的文献
1
Synthesis and biological evaluation of cis-restricted triazole/tetrazole mimics of combretastatin-benzothiazole hybrids as tubulin polymerization inhibitors and apoptosis inducers.作为微管蛋白聚合抑制剂和凋亡诱导剂的柯里拉京-苯并噻唑杂合物的顺式受限三唑/四唑模拟物的合成及生物学评价
Bioorg Med Chem. 2017 Feb 1;25(3):977-999. doi: 10.1016/j.bmc.2016.12.010. Epub 2016 Dec 9.
2
Synthesis of 2-anilinopyridyl-triazole conjugates as antimitotic agents.作为抗有丝分裂剂的2-苯胺基吡啶基-三唑共轭物的合成。
Org Biomol Chem. 2015 May 7;13(17):4879-95. doi: 10.1039/c5ob00232j.
3
Synthesis and biological evaluation of imidazo[1,5-a]pyridine-benzimidazole hybrids as inhibitors of both tubulin polymerization and PI3K/Akt pathway.咪唑并[1,5-a]吡啶-苯并咪唑杂化物作为微管蛋白聚合和PI3K/Akt途径抑制剂的合成及生物学评价
Org Biomol Chem. 2014 Dec 28;12(48):9864-80. doi: 10.1039/c4ob01930j.
4
Structural basis of microtubule stabilization by laulimalide and peloruside A. laulimalide 和 peloruside A 稳定微管的结构基础。
Angew Chem Int Ed Engl. 2014 Feb 3;53(6):1621-5. doi: 10.1002/anie.201307749. Epub 2014 Jan 27.
5
A novel, unusually efficacious duocarmycin carbamate prodrug that releases no residual byproduct.一种新型、高效的双氰胺氨基甲酸酯前药，无残留副产物释放。
J Med Chem. 2012 Jun 28;55(12):5878-86. doi: 10.1021/jm300330b. Epub 2012 Jun 12.
6
Cucurbitacin B induces apoptosis and S phase cell cycle arrest in BEL-7402 human hepatocellular carcinoma cells and is effective via oral administration.葫芦素 B 诱导 BEL-7402 人肝癌细胞凋亡和 S 期细胞周期阻滞，并具有口服有效性。
Cancer Lett. 2010 Aug 1;294(1):118-24. doi: 10.1016/j.canlet.2010.01.029. Epub 2010 Feb 11.
7
Novel cyano- and amidinobenzothiazole derivatives: synthesis, antitumor evaluation, and X-ray and quantitative structure-activity relationship (QSAR) analysis.新型氰基和脒基苯并噻唑衍生物：合成、抗肿瘤评估以及X射线和定量构效关系（QSAR）分析
J Med Chem. 2009 Mar 26;52(6):1744-56. doi: 10.1021/jm801566q.
8
Casticin induces leukemic cell death through apoptosis and mitotic catastrophe.芫花素通过凋亡和有丝分裂灾难诱导白血病细胞死亡。
Ann Hematol. 2009 Aug;88(8):743-52. doi: 10.1007/s00277-008-0677-3. Epub 2009 Jan 13.
9
Seleno-podophyllotoxin derivatives induce hepatoma SMMC-7721 cell apoptosis through Bax pathway.硒代鬼臼毒素衍生物通过Bax途径诱导肝癌SMMC-7721细胞凋亡。
Cell Biol Int. 2008 Feb;32(2):217-23. doi: 10.1016/j.cellbi.2007.08.034. Epub 2007 Sep 20.
10
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.
Zotero 插件