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Mar. Drugs 2019, 17(4), 207; https://doi.org/10.3390/md17040207

Discovery of Natural Dimeric Naphthopyrones as Potential Cytotoxic Agents through ROS-Mediated Apoptotic Pathway

1,†, 1,2,†, 1,3, 4, 1,* and 1,5,*
1
Chinese Academy of Sciences Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China
2
Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao 266042, China
3
College of Resources and Environment, Qingdao Agricultural University, Qingdao 266109, China
4
Technology Center, China Tobacco Henan Industrial Co., Ltd., Zhengzhou, 450000, China
5
State Key Laboratory of Microbial Technology, School of Life Science, Shandong University, No. 72 Binhai Road, Qingdao 266237, China
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Received: 11 March 2019 / Revised: 26 March 2019 / Accepted: 28 March 2019 / Published: 2 April 2019
(This article belongs to the Collection Marine Compounds and Cancer)
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Abstract

A study on the secondary metabolites of Aspergillus sp. XNM-4, which was derived from marine algae Leathesia nana (Chordariaceae), led to the identification of one previously undescribed (1) and seventeen known compounds (218). Their planar structures were established by extensive spectroscopic analyses, while the stereochemical assignments were defined by electronic circular dichroism (ECD) calculations. The biological activities of the compounds were assessed on five human cancer cell lines (PANC-1, A549, MDA-MB-231, Caco-2, and SK-OV-3), and one human normal cell line (HL-7702) using an MTT [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide] assay. Among them, the dimeric naphthopyrones 7, 10 and 12 exhibited potent cytotoxicity. Further mechanism studies showed that 12 induced apoptosis, arrested the cell cycle at the G0/G1 phase in the PANC-1 cells, caused morphological changes and generated ROS; and it induces PANC-1 cells apoptosis via ROS-mediated PI3K/Akt signaling pathway. View Full-Text
Keywords: Aspergillus; naphthopyrones; cytotoxicity; endophytic fungus; Leathesia nana Aspergillus; naphthopyrones; cytotoxicity; endophytic fungus; Leathesia nana
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Xu, K.; Guo, C.; Meng, J.; Tian, H.; Guo, S.; Shi, D. Discovery of Natural Dimeric Naphthopyrones as Potential Cytotoxic Agents through ROS-Mediated Apoptotic Pathway. Mar. Drugs 2019, 17, 207.

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