Synthesis and evaluation of new 2-chloro-4-aminopyrimidine and 2,6-dimethyl-4-aminopyrimidine derivatives as tubulin polymerization inhibitors
| Autor: | Xingshu Li, Shaoyu Xu, Xian Jia, Baijiao An, Yuxin Li, Luo Xunbang |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Clinical Biochemistry Compound 17 Pharmaceutical Science Antineoplastic Agents Apoptosis Biochemistry Microtubules Tubulin Polymerization Inhibitors Polymerization 03 medical and health sciences Structure-Activity Relationship 0302 clinical medicine Microtubule Tubulin Cell Line Tumor Drug Discovery Binding pattern medicine Humans Molecular Biology Cell Proliferation Dose-Response Relationship Drug Molecular Structure Chemistry Organic Chemistry Cancer medicine.disease Tubulin Modulators Mitochondria Molecular Docking Simulation 030104 developmental biology Pyrimidines Cell culture 030220 oncology & carcinogenesis Molecular Medicine Drug Screening Assays Antitumor Human cancer |
| Zdroj: | Bioorganicmedicinal chemistry letters. 28(10) |
| ISSN: | 1464-3405 |
| Popis: | Eighteen new 2-chloro-4-aminopyrimidine and 2,6-dimethyl-4-aminopyrimidine derivatives were synthesized and evaluated as tubulin polymerization inhibitor for the treatment of cancer. Among them, compounds 10, 17, 20 and 21 exhibited potent antiproliferative activities against five human cancer cell lines. Microtubule dynamics assay showed that compound 17 could effectively inhibit tubulin polymerization. Molecular docking studies were also carried out to understand the binding pattern. Further mechanism studies revealed that 17 could induce G2/M phase arrest, disrupt the organization of the cellular microtubule network and induce cell apoptosis and mitochondrial dysfunction. |
| Databáze: | OpenAIRE |
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