Integrating Activity-Guided Strategy and Fingerprint Analysis to Target Potent Cytotoxic Brefeldin A from a Fungal Library of the Medicinal Mangrove <i>Acanthus ilicifolius</i>
Cui-Fang Wang,
Jie Ma,
Qian-Qian Jing,
Xi-Zhen Cao,
Lu Chen,
Rong Chao,
Ji-Yong Zheng,
Chang-Lun Shao,
Xiao-Xi He,
Mei-Yan Wei
Affiliations
Cui-Fang Wang
Key Laboratory of Marine Drugs, The Ministry of Education of China, School of Medicine and Pharmacy, College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China
Jie Ma
Key Laboratory of Marine Drugs, The Ministry of Education of China, School of Medicine and Pharmacy, College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China
Qian-Qian Jing
Key Laboratory of Marine Drugs, The Ministry of Education of China, School of Medicine and Pharmacy, College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China
Xi-Zhen Cao
Key Laboratory of Marine Drugs, The Ministry of Education of China, School of Medicine and Pharmacy, College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China
Lu Chen
Key Laboratory of Marine Drugs, The Ministry of Education of China, School of Medicine and Pharmacy, College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China
Rong Chao
Key Laboratory of Marine Drugs, The Ministry of Education of China, School of Medicine and Pharmacy, College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China
Ji-Yong Zheng
State Key Laboratory for Marine Corrosion and Protection, Luoyang Ship Material Research Institute (LSMRI), Qingdao 266061, China
Chang-Lun Shao
Key Laboratory of Marine Drugs, The Ministry of Education of China, School of Medicine and Pharmacy, College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China
Xiao-Xi He
Key Laboratory of Marine Drugs, The Ministry of Education of China, School of Medicine and Pharmacy, College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China
Mei-Yan Wei
Key Laboratory of Marine Drugs, The Ministry of Education of China, School of Medicine and Pharmacy, College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China
Mangrove-associated fungi are rich sources of novel and bioactive compounds. A total of 102 fungal strains were isolated from the medicinal mangrove Acanthus ilicifolius collected from the South China Sea. Eighty-four independent culturable isolates were identified using a combination of morphological characteristics and internal transcribed spacer (ITS) sequence analyses, of which thirty-seven strains were selected for phylogenetic analysis. The identified fungi belonged to 22 genera within seven taxonomic orders of one phyla, of which four genera Verticillium, Neocosmospora, Valsa, and Pyrenochaeta were first isolated from mangroves. The cytotoxic activity of organic extracts from 55 identified fungi was evaluated against human lung cancer cell lines (A-549), human cervical carcinoma cell lines (HeLa), human hepatoma cells (HepG2), and human acute lymphoblastic leukemia cell lines (Jurkat). The crude extracts of 31 fungi (56.4%) displayed strong cytotoxicity at the concentration of 50 μg/mL. Furthermore, the fungus Penicillium sp. (HS-N-27) still showed strong cytotoxic activity at the concentration of 25 µg/mL. Integrating cytotoxic activity-guided strategy and fingerprint analysis, a well-known natural Golgi-disruptor and Arf-GEFs inhibitor, brefeldin A, was isolated from the target active strain HS-N-27. It displayed potential activity against A549, HeLa and HepG2 cell lines with the IC50 values of 101.2, 171.9 and 239.1 nM, respectively. Therefore, combining activity-guided strategy with fingerprint analysis as a discovery tool will be implemented as a systematic strategy for quick discovery of active compounds.
