Synthesis, biological evaluation, and structure-activity relationships of new tubulin polymerization inhibitors based on 5-amino-1,2,4-triazole scaffold
| Autor: | You Wenwei, Xiao-Lan Zheng, Jin-Mei Lai, Xiong-Li Li, Li-Yuan Wei, Fang Yang, Xie-Er Jian, Lin Chen, Dong-Xin Lv, Pei-Liang Zhao, Yu-Xia Liu, Li-Li Yuan, Feng-Ting Liang |
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| Rok vydání: | 2020 |
| Předmět: |
Scaffold
Molecular model Clinical Biochemistry Pharmaceutical Science Antineoplastic Agents 01 natural sciences Biochemistry Tubulin Polymerization Inhibitors Polymerization HeLa chemistry.chemical_compound Structure-Activity Relationship Tubulin Drug Discovery Moiety Humans Molecular Biology IC50 Cell Proliferation biology Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry Organic Chemistry 1 2 4-Triazole Cell Cycle Checkpoints Triazoles biology.organism_classification Tubulin Modulators 0104 chemical sciences 010404 medicinal & biomolecular chemistry chemistry biology.protein Molecular Medicine Drug Screening Assays Antitumor HeLa Cells |
| Zdroj: | Bioorganicmedicinal chemistry letters. 38 |
| ISSN: | 1464-3405 |
| Popis: | Based on our previous research, thirty new 5-amino-1H-1,2,4-triazoles possessing 3,4,5-trimethoxyphenyl moiety were synthesized, and evaluated for antiproliferative activities. Among them, compounds IIa, IIIh, and IIIm demonstrated significant antiproliferative activities against a panel of tumor cell lines, and the promising compound IIIm dose-dependently caused G2/M phase arrest in HeLa cells. Furthermore, analogue IIa exhibited the most potent tubulin polymerization inhibitory activity with an IC50 value of 9.4 μM, and molecular modeling studies revealed that IIa formed stable interactions in the colchicine-binding site of tubulin, suggesting that 5-amino-1H-1,2,4-triazole scaffold has potential for further investigation to develop novel tubulin polymerization inhibitors with anticancer activity. |
| Databáze: | OpenAIRE |
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