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Antimalarial Peptide and Polyketide Natural Products from the Fijian Marine Cyanobacterium Moorea producens

1
School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332, USA
2
Calibr, a division of The Scripps Research Institute, La Jolla, CA 92037, USA
3
School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA 30332, USA
4
Institute of Applied Sciences, University of the South Pacific, Suva, Fiji
5
Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332, USA
6
Center for Microbial Dynamics and Infection, Georgia Institute of Technology, Atlanta, GA 30332, USA
*
Author to whom correspondence should be addressed.
Mar. Drugs 2020, 18(3), 167; https://doi.org/10.3390/md18030167
Received: 20 February 2020 / Revised: 12 March 2020 / Accepted: 16 March 2020 / Published: 18 March 2020
(This article belongs to the Special Issue Compounds from Cyanobacteria III)
A new cyclic peptide, kakeromamide B (1), and previously described cytotoxic cyanobacterial natural products ulongamide A (2), lyngbyabellin A (3), 18E-lyngbyaloside C (4), and lyngbyaloside (5) were identified from an antimalarial extract of the Fijian marine cyanobacterium Moorea producens. Compound 1 exhibited moderate activity against Plasmodium falciparum blood-stages with an EC50 value of 8.9 µM whereas 2 and 3 were more potent with EC50 values of 0.99 µM and 1.5 nM, respectively. Compounds 1, 4, and 5 displayed moderate liver-stage antimalarial activity against P. berghei liver schizonts with EC50 values of 11, 7.1, and 4.5 µM, respectively. The threading-based computational method FINDSITEcomb2.0 predicted the binding of 1 and 2 to potentially druggable proteins of Plasmodium falciparum, prompting formulation of hypotheses about possible mechanisms of action. Kakeromamide B (1) was predicted to bind to several Plasmodium actin-like proteins and a sortilin protein suggesting possible interference with parasite invasion of host cells. When 1 was tested in a mammalian actin polymerization assay, it stimulated actin polymerization in a dose-dependent manner, suggesting that 1 does, in fact, interact with actin. View Full-Text
Keywords: marine; cyanobacteria; malaria; mechanism of action; natural product marine; cyanobacteria; malaria; mechanism of action; natural product
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MDPI and ACS Style

Sweeney-Jones, A.M.; Gagaring, K.; Antonova-Koch, J.; Zhou, H.; Mojib, N.; Soapi, K.; Skolnick, J.; McNamara, C.W.; Kubanek, J. Antimalarial Peptide and Polyketide Natural Products from the Fijian Marine Cyanobacterium Moorea producens. Mar. Drugs 2020, 18, 167.

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