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Please use this identifier to cite or link to this item: http://ntour.ntou.edu.tw:8080/ir/handle/987654321/45912

Title: Miniaturized cultivation of microbiota for antimalarial drug discovery.
Authors: Carrie Waterman
Laurent Calcul
Jeremy Beau
Wai Sheung Ma
Matthew D. Lebar Jacqueline L. von Salm
Charles Harter
Tina Mutka
Lindsay C. Morton
Patrick Maignan
Betty Barisic Alberto van Olphen
Dennis E. Kyle
Lilian Vrijmoed
Ka‐Lai Pang
Cedric J. Pearce
Bill J. Baker
Contributors: 國立臺灣海洋大學:海洋生物研究所
Keywords: natural products
high‐throughput screening
endophytes
malaria
microbe cultivation
Date: 2016
Issue Date: 2018-04-17T06:18:22Z
Publisher: Medicinal Research Reviews
Abstract: Abstract: The ongoing search for effective antiplasmodial agents remains essential in the fight against malaria worldwide. Emerging parasitic drug resistance places an urgent need to explore chemotherapies with novel structures and mechanisms of action. Natural products have historically provided effective antimalarial drug scaffolds. In an effort to search nature's chemical potential for antiplasmodial agents, unconventionally sourced organisms coupled with innovative cultivation techniques were utilized. Approximately 60,000 niche microbes from various habitats (slow‐growing terrestrial fungi, Antarctic microbes, and mangrove endophytes) were cultivated on a small‐scale, extracted, and used in high‐throughput screening to determine antimalarial activity. About 1% of crude extracts were considered active and 6% partially active (≥67% inhibition at 5 and 50 μg/mL, respectively). Active extracts (685) were cultivated on a large‐scale, fractionated, and screened for both antimalarial activity and cytotoxicity. High interest fractions (397) with an IC50 < 1.11 μg/mL were identified and subjected to chromatographic separation for compound characterization and dereplication. Identifying active compounds with nanomolar antimalarial activity coupled with a selectivity index tenfold higher was accomplished with two of the 52 compounds isolated. This microscale, high‐throughput screening project for antiplasmodial agents is discussed in the context of current natural product drug discovery efforts.
Relation: 36(1) pp.144-68
URI: http://ntour.ntou.edu.tw:8080/ir/handle/987654321/45912
Appears in Collections:[海洋生物研究所] 期刊論文

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