基于端粒G-四链体结构的三阴性乳腺癌细胞抑制剂的虚拟筛选

doi:10.5246/jcps.2020.06.036

中国药学(英文版) ›› 2020, Vol. 29 ›› Issue (6): 383-389.DOI: 10.5246/jcps.2020.06.036

基于端粒G-四链体结构的三阴性乳腺癌细胞抑制剂的虚拟筛选

邓华⁺, 高超⁺, 位灯国^*, 刘思思^*

华中农业大学理学院, 湖北武汉 430070

收稿日期:2019-12-30 修回日期:2020-02-13 出版日期:2020-06-30 发布日期:2020-03-18
通讯作者: Tel.: +86-27-87282133, E-mail: dgwei@mail.hzau.edu.cn; liusisi@mail.hzau.edu.cn
基金资助:
National Natural Science Foundation of China (Grant No. 31701791, 21732002, 31672558 and 21502060), Huazhong Agricultural University Scientific & Technological Self-innovation Foundation (Grant No. 2662017PY113, 2015RC013 and 2662015PY208), Open fund of The State Key Laboratory of Bio-organic and Natural Products Chemistry, CAS (Grant No. SKLBNPC16343).

Virtual screening for triple-negative breast cancer cell inhibitors based on telomere G-quadruplex structure

Hua Deng⁺, Chao Gao⁺, Dengguo Wei^*, Sisi Liu^*

Department of Chemistry, College of Science, Huazhong Agricultural University, Wuhan 430070, China

Received:2019-12-30 Revised:2020-02-13 Online:2020-06-30 Published:2020-03-18
Contact: Tel.: +86-27-87282133, E-mail: dgwei@mail.hzau.edu.cn; liusisi@mail.hzau.edu.cn
Supported by:
National Natural Science Foundation of China (Grant No. 31701791, 21732002, 31672558 and 21502060), Huazhong Agricultural University Scientific & Technological Self-innovation Foundation (Grant No. 2662017PY113, 2015RC013 and 2662015PY208), Open fund of The State Key Laboratory of Bio-organic and Natural Products Chemistry, CAS (Grant No. SKLBNPC16343).

摘要/Abstract

摘要：

三阴性乳腺癌是乳腺癌中最具侵略性的亚型, 经常对化疗药物产生耐药性。靶向该肿瘤相关基因的G-四链体结构, 有望开发出新的抗肿瘤药物。本研究靶向21-mer端粒G-四链体结构, 通过基于结构的高通量虚拟筛选, 得到可稳定端粒G-四链体的化合物VB07和VC02。细胞毒性实验表明, VB07和VC02在5 μM的浓度下对三阴性乳腺癌细胞具有抑制作用。这项研究表明基于结构的高通量虚拟筛选可以成功地发现靶向端粒G-四链体的化合物, 并利用此方法发现可抑制三阴性乳腺癌细胞的新化合物。

关键词: 三阴性乳腺癌, 端粒G-四链体, 基于结构的虚拟筛选, 抗癌药物

Abstract:

Triple-negative breast cancer is an aggressive subtype that frequently develops resistance to chemotherapy. It is expectedto develop new anti-tumor drugs through targeting the structure of G-quadruplexes of the genes associated with this tumor. In this work, by targeting the 21-mer telomere G-quadruplex structure, compounds VB07 and VC02 were identified to stabilize the telomere G-quadruplex through structure-based high-throughput virtual screening. Cell cytotoxicity assay showed that VB07 and VC02 exhibited inhibitory effect on triple-negative breast cancer cells at the concentration of 5 μM. This study showed that structure-based high-throughput virtual screening was able to successfully identify the proper compounds targeting the telomere G-quadruplex, which exhibited inhibitory effects against thetriple-negative breast cancer cells.

Key words: Triple-negative breast cancer, Telomere G-quadruplex, Structure-based virtual screening, Anti-cancer drug

中图分类号:

R966

Supporting:

邓华, 高超, 位灯国, 刘思思. 基于端粒G-四链体结构的三阴性乳腺癌细胞抑制剂的虚拟筛选[J]. 中国药学(英文版), 2020, 29(6): 383-389.

Hua Deng, Chao Gao, Dengguo Wei, Sisi Liu. Virtual screening for triple-negative breast cancer cell inhibitors based on telomere G-quadruplex structure[J]. Journal of Chinese Pharmaceutical Sciences, 2020, 29(6): 383-389.

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基于端粒G-四链体结构的三阴性乳腺癌细胞抑制剂的虚拟筛选

Virtual screening for triple-negative breast cancer cell inhibitors based on telomere G-quadruplex structure

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