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Mar. Drugs 2017, 15(7), 217; doi:10.3390/md15070217

Discovery of DNA Topoisomerase I Inhibitors with Low-Cytotoxicity Based on Virtual Screening from Natural Products

1
Key Laboratory of Marine Drugs, The Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China
2
Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266071, China
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Received: 22 April 2017 / Revised: 28 June 2017 / Accepted: 5 July 2017 / Published: 9 July 2017
(This article belongs to the Collection Marine Compounds and Cancer)
View Full-Text   |   Download PDF [3181 KB, uploaded 9 July 2017]   |  

Abstract

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. View Full-Text
Keywords: virtual screening; molecular docking; Topo I inhibitor; low toxic; natural product virtual screening; molecular docking; Topo I inhibitor; low toxic; natural product
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Xin, L.-T.; Liu, L.; Shao, C.-L.; Yu, R.-L.; Chen, F.-L.; Yue, S.-J.; Wang, M.; Guo, Z.-L.; Fan, Y.-C.; Guan, H.-S.; Wang, C.-Y. Discovery of DNA Topoisomerase I Inhibitors with Low-Cytotoxicity Based on Virtual Screening from Natural Products. Mar. Drugs 2017, 15, 217.

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