Miniaturized Cultivation of Microbiota for Antimalarial Drug Discovery.

Autor: Waterman C; Department of Chemistry, University of South Florida, Tampa, Florida, 33620, USA., Calcul L; Department of Chemistry, University of South Florida, Tampa, Florida, 33620, USA., Beau J; Department of Chemistry, University of South Florida, Tampa, Florida, 33620, USA., Ma WS; Department of Chemistry, University of South Florida, Tampa, Florida, 33620, USA., Lebar MD; Department of Chemistry, University of South Florida, Tampa, Florida, 33620, USA., von Salm JL; Department of Chemistry, University of South Florida, Tampa, Florida, 33620, USA., Harter C; Department of Chemistry, University of South Florida, Tampa, Florida, 33620, USA., Mutka T; Department of Global Health, University of South Florida, Tampa, Florida, 33620, USA., Morton LC; Department of Global Health, University of South Florida, Tampa, Florida, 33620, USA., Maignan P; Department of Global Health, University of South Florida, Tampa, Florida, 33620, USA., Barisic B; Department of Global Health, University of South Florida, Tampa, Florida, 33620, USA., van Olphen A; Department of Global Health, University of South Florida, Tampa, Florida, 33620, USA., Kyle DE; Department of Global Health, University of South Florida, Tampa, Florida, 33620, USA., Vrijmoed L; Department of Biology and Chemistry, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong., Pang KL; Institute of Marine Biology and Center of Excellence for the Oceans, National Taiwan Ocean University, Keelung, 20224, Taiwan., Pearce CJ; Mycosynthetix Inc, Hillsborough, North Carolina, 27278, USA., Baker BJ; Department of Chemistry, University of South Florida, Tampa, Florida, 33620, USA.; Center for Drug Discovery and Innovation, University of South Florida, Tampa, Florida, 36612, USA.
Jazyk: angličtina
Zdroj: Medicinal research reviews [Med Res Rev] 2016 Jan; Vol. 36 (1), pp. 144-68. Date of Electronic Publication: 2014 Dec 26.
DOI: 10.1002/med.21335
Abstrakt: 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.
(© 2014 Wiley Periodicals, Inc.)
Databáze: MEDLINE
Externí odkaz: