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含三甲氧基苯基骨架的具有抗增殖作用的苯并噻唑类化合物，作为新型秋水仙碱结合位点微管蛋白聚合抑制剂。

Antiproliferative benzothiazoles incorporating a trimethoxyphenyl scaffold as novel colchicine site tubulin polymerisation inhibitors.

机构信息

Modern Research Center for Traditional Chinese Medicine, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, People's Republic of China.

Department of Gastroenterology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China.

出版信息

J Enzyme Inhib Med Chem. 2020 Dec;35(1):1050-1059. doi: 10.1080/14756366.2020.1753721.

DOI:10.1080/14756366.2020.1753721
PMID:32299262
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7178834/
Abstract

Tubulin polymerisation inhibitors exhibited an important role in the treatment of patients with prostate cancer. Herein, we reported the medicinal chemistry efforts leading to a new series of benzothiazoles by a bioisosterism approach. Biological testing revealed that compound could significantly inhibit tubulin polymerisation of a concentration dependent manner, with an IC value of 2.87 μM. Immunofluorescence and EBI competition assay investigated that compound effectively inhibited tubulin polymerisation and directly bound to the colchicine-binding site of β-tubulin in PC3 cells. Docking analysis showed that formed hydrogen bonds with residues Tyr357, Ala247 and Val353 of tubulin. Importantly, it displayed the promising antiproliferative ability against C42B, LNCAP, 22RV1 and PC3 cells with IC values of 2.81 μM, 4.31 μM, 2.13 μM and 2.04 μM, respectively. In summary, compound was a novel colchicine site tubulin polymerisation inhibitor with potential to treat prostate cancer.

摘要

微管聚合抑制剂在治疗前列腺癌患者方面发挥了重要作用。在此，我们通过生物等排方法报告了导致一系列新苯并噻唑的药物化学研究。生物测试显示，化合物 能够以浓度依赖的方式显著抑制 微管聚合，IC 值为 2.87 μM。免疫荧光和 EBI 竞争测定表明，化合物 能够有效抑制微管聚合，并直接与 PC3 细胞中 β-微管的秋水仙碱结合位点结合。对接分析表明， 与微管的残基 Tyr357、Ala247 和 Val353 形成氢键。重要的是，它对 C42B、LNCAP、22RV1 和 PC3 细胞表现出有希望的增殖抑制能力，IC 值分别为 2.81 μM、4.31 μM、2.13 μM 和 2.04 μM。总之，化合物 是一种新型的秋水仙碱结合位点微管聚合抑制剂，具有治疗前列腺癌的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb20/7178834/b05eb8bf9249/IENZ_A_1753721_F0007_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb20/7178834/810bc90c8d8b/IENZ_A_1753721_UF0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb20/7178834/20ad309f28b6/IENZ_A_1753721_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb20/7178834/23254e44e50c/IENZ_A_1753721_F0002_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb20/7178834/d13633db2498/IENZ_A_1753721_SCH0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb20/7178834/8c6e237d193b/IENZ_A_1753721_F0003_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb20/7178834/b30ee63bf841/IENZ_A_1753721_F0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb20/7178834/b1a309a44b17/IENZ_A_1753721_F0005_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb20/7178834/e49536250503/IENZ_A_1753721_F0006_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb20/7178834/b05eb8bf9249/IENZ_A_1753721_F0007_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb20/7178834/810bc90c8d8b/IENZ_A_1753721_UF0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb20/7178834/20ad309f28b6/IENZ_A_1753721_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb20/7178834/23254e44e50c/IENZ_A_1753721_F0002_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb20/7178834/d13633db2498/IENZ_A_1753721_SCH0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb20/7178834/8c6e237d193b/IENZ_A_1753721_F0003_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb20/7178834/b30ee63bf841/IENZ_A_1753721_F0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb20/7178834/b1a309a44b17/IENZ_A_1753721_F0005_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb20/7178834/e49536250503/IENZ_A_1753721_F0006_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb20/7178834/b05eb8bf9249/IENZ_A_1753721_F0007_C.jpg

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