Integrating Activity-Guided Strategy and Fingerprint Analysis to Target Potent Cytotoxic Brefeldin A from a Fungal Library of the Medicinal Mangrove Acanthus ilicifolius.
Integrating Activity-Guided Strategy and Fingerprint Analysis to Target Potent Cytotoxic Brefeldin A from a Fungal Library of the Medicinal Mangrove Acanthus ilicifolius.
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整合活动引导策略和指纹分析，从药用红树林 Acanthus ilicifolius 真菌库中靶向有效的细胞毒性布雷菲德菌素 A
作者：
红树林伴生真菌是新的生物活性化合物的丰富来源。从中国南海药用红树林老鼠仓（Acanthus ilicifolius）中分离到102株真菌。84个独立的可培养的菌株进行了鉴定，使用的形态特征和内部转录间隔区（ITS）序列分析，其中37株进行了系统发育分析。鉴定出的真菌隶属于1门7个分类目22属，其中轮枝菌属、新cosmospora属、腐壳菌属和核壳菌属4个属为首次从红树林中分离得到。评价了55种已鉴定真菌的有机提取物对人肺癌细胞系（A-549）、人宫颈癌细胞系（HeLa）、人肝癌细胞系（HepG 2）和人急性淋巴细胞白血病细胞系（Jurkat）的细胞毒活性。31株真菌（56.4%）的粗提物在浓度为50 μg/mL时表现出较强的细胞毒活性。此外，真菌青霉菌（HS-N-27）在25 µg/mL浓度下仍显示出较强的细胞毒活性。结合细胞毒活性导向策略和指纹图谱分析，从目标活性菌株HS-N-27中分离得到一种已知的天然高尔基体破坏剂和Arf-GEFs抑制剂布雷菲德菌素A。它对A549、HeLa和HepG 2细胞系显示出潜在的活性，IC 50值分别为101.2、171.9和239.1 nM。因此，将活性导向策略与指纹分析相结合作为发现工具将被实施为快速发现活性化合物的系统策略。
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.
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影响因子：
5.4
作者：
Ancheeva E;Daletos G;Proksch P
通讯作者：
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影响因子：
5.4
作者：
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通讯作者：
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影响因子：
64.8
作者：
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通讯作者：
Cherfils, J
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影响因子：
3
作者：
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通讯作者：
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影响因子：
14.5
作者：
Mohan，Chakrabhavi Dhananjaya;Rangappa，Shobith;Rangappa，Kanchugarakoppal S.
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Rangappa，Kanchugarakoppal S.