Design, synthesis and biological evaluation of novel homocamptothecin analogues as potent antitumor agents
| Autor: | Shao Xie, Yi Chen, Longjun Ma, Lei Wang, Wei Lu |
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| Rok vydání: | 2015 |
| Předmět: |
Clinical Biochemistry
Pharmaceutical Science Antineoplastic Agents Pharmacology Biochemistry Mice Structure-Activity Relationship Drug Discovery Animals Humans Molecular Biology Cell Proliferation Biological evaluation chemistry.chemical_classification Antitumor activity Dose-Response Relationship Drug Molecular Structure Organic Chemistry Neoplasms Experimental Xenograft Model Antitumor Assays Human colon cancer Water soluble chemistry Design synthesis Cell culture Drug Design Molecular Medicine Camptothecin Homocamptothecin HT29 Cells Lactone |
| Zdroj: | Bioorganic & Medicinal Chemistry. 23:1950-1962 |
| ISSN: | 0968-0896 |
| DOI: | 10.1016/j.bmc.2015.03.031 |
| Popis: | Fifteen novel homocamptothecin derivatives with α-OMe substituted E-rings were designed and synthesized. All of the derivatives exhibited similar or superior cytotoxicities compared with that of SN-38, and they inhibited Topo I activity in a cell-free assay in a manner similar to that of SN-38, confirming that they represent a new class of Topo I inhibitors. Notably, the water soluble compound 36o (1.2 mg/mL) exhibited increased lactone stability, and at 0.5 mg/kg and 3.0 mg/kg, it demonstrated significant antitumor activity in mice bearing a xenograft model using human colon cancer cell line HT-29. On the basis of these positive results, further development of 36o-related compounds as potential anticancer clinical trial candidates is definitely warranted. |
| Databáze: | OpenAIRE |
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