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Mar. Drugs 2013, 11(12), 5036-5050; doi:10.3390/md11125036

Screening Mangrove Endophytic Fungi for Antimalarial Natural Products

1
Department of Chemistry, University of South Florida, 4202 E. Fowler, CHE 205, Tampa, FL 33620, USA
2
Department of Global Health, University of South Florida, 3720 Spectrum Blvd., Suite 304,Tampa, FL 33612, USA
3
Department of Biology and Chemistry, City University of Hong Kong, 83 Tat Chee Avenue, Hong Kong, China
4
Institute of Marine Biology and Center of Excellence for the Oceans, National Taiwan Ocean University, 2 Pei-Ning Road, Keelung 20224, Taiwan
5
Mycosynthetix, Inc., 505 Meadowlands Drive, Suite 103, Hillsborough, NC 27278, USA
6
Center for Drug Discovery and Innovation, University of South Florida, 3720 Spectrum Blvd., Suite 303, Tampa, FL 33612, USA
*
Author to whom correspondence should be addressed.
Received: 12 September 2013 / Revised: 27 November 2013 / Accepted: 28 November 2013 / Published: 12 December 2013
(This article belongs to the Special Issue Antiprotozoal Marine Natural Products)
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Abstract

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 (1416, 18) were isolated including a new dimeric tetrahydroxanthone, dicerandrol D (14), which was found to display the most favorable bioactivity profile.
Keywords: fungi; endophytes; mangroves; malaria; cytotoxicity; high-throughput fungi; endophytes; mangroves; malaria; cytotoxicity; high-throughput
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

Calcul, L.; Waterman, C.; Ma, W.S.; Lebar, M.D.; Harter, C.; Mutka, T.; Morton, L.; Maignan, P.; Olphen, A.V.; Kyle, D.E.; Vrijmoed, L.; Pang, K.-L.; Pearce, C.; Baker, B.J. Screening Mangrove Endophytic Fungi for Antimalarial Natural Products. Mar. Drugs 2013, 11, 5036-5050.

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