期刊
MARINE DRUGS
卷 15, 期 7, 页码 -出版社
MDPI
DOI: 10.3390/md15070217
关键词
virtual screening; molecular docking; Topo I inhibitor; low toxic; natural product
资金
- National High Technology Research and Development Program of China (863 Program) [2013AA093001]
- Qingdao National Laboratory for Marine Science and Technology [2015ASKJ02]
- Taishan Scholars Program, China
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 mu M. 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.
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