Synthesis and anticancer activity of novel rapamycin C-28 containing triazole moiety compounds
| Autor: | Yu Hui, XueHui Huang, Yubing Lv, Huang Qingwen, Ying Jiayin, Yuanrong Cheng, Zheng Congshen, Xie Lijun, Chen Xiaoming, Jie Huang |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cell cycle checkpoint Triazole Pharmaceutical Science Antineoplastic Agents Apoptosis Pharmacology Structure-Activity Relationship 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Drug Discovery Tumor Cells Cultured medicine Humans Phosphorylation Protein Kinase Inhibitors PI3K/AKT/mTOR pathway Cell Proliferation Sirolimus A549 cell Everolimus Dose-Response Relationship Drug Molecular Structure Kinase TOR Serine-Threonine Kinases Cell Cycle Checkpoints Triazoles Temsirolimus 030104 developmental biology chemistry 030220 oncology & carcinogenesis Drug Screening Assays Antitumor Signal Transduction medicine.drug |
| Zdroj: | Archiv der Pharmazie. 351:1800123 |
| ISSN: | 0365-6233 |
| Popis: | Rapamycin is an mTOR allosteric inhibitor with multiple functions such as immunosuppressive, anticancer, and lifespan prolonging activities. Its C-43 semi-synthetic derivatives temsirolimus and everolimus have been used as mTOR targeting anticancer drugs in the clinic. Following our previous research on antitumor rapalogs modified on the C-43 position, 13 novel rapamycin triazole hybrids (6a-g, 7a-f) were designed and synthesized on the C-28 position of rapamycin via Huisgen's reaction. Anticancer assays indicated that the targeted derivatives containing phenyl and 4-methylphenyl groups showed an obvious raise in anticancer activity. On the contrary, the compounds with methoxyl, amine, and halogen groups on the benzene ring displayed lower anticancer activity. Compound 6c, as the most active compound, showed a stronger inhibition effect as compared with rapamycin for almost all of the tested cell lines (p |
| Databáze: | OpenAIRE |
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