Screening mangrove endophytic fungi for antimalarial natural products.

Screening mangrove endophytic fungi for antimalarial natural products.
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DOI:
10.3390/md11125036
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发表时间:
2013-12-12
期刊:
影响因子:
5.4
通讯作者:
Baker BJ
Baker BJ
中科院分区:
医学2区
文献类型:
--
作者:
Calcul L;Waterman C;Ma WS;Lebar MD;Harter C;Mutka T;Morton L;Maignan P;Van Olphen A;Kyle DE;Vrijmoed L;Pang KL;Pearce C;Baker BJ

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我们进行了一项筛选活动,以调查真菌作为新的抗疟化合物的来源。我们的真菌收集的一个子集,包括中国红树林内生菌提供了超过5000亲脂性提取物。我们开发了一个基于小规模培养的加速发现计划,用于粗提物筛选和高通量疟疾检测。开发了命中的标准,并对高优先级命中进行了放大培养。将来自大规模培养的提取物分级分离,并对这些级分进行体外疟疾和细胞毒性筛选。开发了推进馏分纯化的标准,包括引入选择性指数和已知代谢物的去复制。从中国红树林内生菌中分离得到4个新化合物(14-16,18),其中包括一个新的二聚四羟基蒽酮,dicerandrol D(14),该化合物显示出最好的生物活性。
We conducted a screening campaign to investigate fungi as a source for new antimalarial compounds. A subset of our fungal collection comprising Chinese mangrove endophytes provided over 5000 lipophilic extracts. We developed an accelerated discovery program based on small-scale cultivation for crude extract screening and a high-throughput malaria assay. Criteria for hits were developed and high priority hits were subjected to scale-up cultivation. Extracts from large scale cultivation were fractionated and these fractions subjected to both in vitro malaria and cytotoxicity screening. Criteria for advancing fractions to purification were developed, including the introduction of a selectivity index and by dereplication of known metabolites. From the Chinese mangrove endophytes, four new compounds (14–16, 18) were isolated including a new dimeric tetrahydroxanthone, dicerandrol D (14), which was found to display the most favorable bioactivity profile.
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