Discovery of DNA Topoisomerase I Inhibitors with Low-Cytotoxicity Based on Virtual Screening from Natural Products
| Autor: | Zhong-Long Guo, Ya-Chu Fan, Hua-Shi Guan, Lan-Ting Xin, Shi-Jun Yue, Chang-Yun Wang, Rilei Yu, Mei Wang, Fangling Chen, Lu Liu, Chang-Lun Shao |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
natural product Stereochemistry Pharmaceutical Science Antineoplastic Agents Biology 01 natural sciences Article Topo I inhibitor Structure-Activity Relationship 03 medical and health sciences chemistry.chemical_compound Drug Discovery Animals Humans Cytotoxic T cell Bioassay Cytotoxicity lcsh:QH301-705.5 Pharmacology Toxicology and Pharmaceutics (miscellaneous) DNA Topoisomerase I Inhibitors Biological Products Virtual screening Natural product 010405 organic chemistry Fungi molecular docking Plants Anthozoa virtual screening low toxic 0104 chemical sciences 030104 developmental biology lcsh:Biology (General) DNA Topoisomerases Type I chemistry Biochemistry Docking (molecular) DNA supercoil Topoisomerase I Inhibitors |
| Zdroj: | Marine Drugs Volume 15 Issue 7 Pages: 217 Marine Drugs, Vol 15, Iss 7, p 217 (2017) |
| ISSN: | 1660-3397 |
| DOI: | 10.3390/md15070217 |
| Popis: | Currently, DNA topoisomerase I (Topo I) inhibitors constitute a family of antitumor agents with demonstrated clinical effects on human malignancies. However, the clinical uses of these agents have been greatly limited due to their severe toxic effects. Therefore, it is urgent to find and develop novel low toxic Topo I inhibitors. In recent years, during our ongoing research on natural antitumor products, a collection of low cytotoxic or non-cytotoxic compounds with various structures were identified from marine invertebrates, plants, and their symbiotic microorganisms. In the present study, new Topo I inhibitors were discovered from low cytotoxic and non-cytotoxic natural products by virtual screening with docking simulations in combination with bioassay test. In total, eight potent Topo I inhibitors were found from 138 low cytotoxic or non-cytotoxic compounds from coral-derived fungi and plants. All of these Topo I inhibitors demonstrated activities against Topo I-mediated relaxation of supercoiled DNA at the concentrations of 5–100 µM. Notably, the flavonoids showed higher Topo I inhibitory activities than other compounds. These newly discovered Topo I inhibitors exhibited structurally diverse and could be considered as a good starting point for the development of new antitumor lead compounds. |
| Databáze: | OpenAIRE |
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