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. 2020 Mar 31;25(7):1604.
doi: 10.3390/molecules25071604.

Palstimolide A: A Complex Polyhydroxy Macrolide with Antiparasitic Activity

Affiliations

Palstimolide A: A Complex Polyhydroxy Macrolide with Antiparasitic Activity

Lena Keller et al. Molecules. .

Abstract

Marine Cyanobacteria (blue-green algae) have been shown to possess an enormous potential to produce structurally diverse natural products that exhibit a broad spectrum of potent biological activities, including cytotoxic, antifungal, antiparasitic, antiviral, and antibacterial activities. Here, we report the isolation and structure determination of palstimolide A, a complex polyhydroxy macrolide with a 40-membered ring that was isolated from a tropical marine cyanobacterium collected at Palmyra Atoll. NMR-guided fractionation in combination with MS2-based molecular networking and isolation via HPLC yielded 0.7 mg of the pure compound. The small quantity isolated along with the presence of significant signal degeneracy in both the 1H and 13C-NMR spectra complicated the structure elucidation of palstimolide A. Various NMR experiments and solvent systems were employed, including the LRHSQMBC experiment that allows the detection of long-range 1H-13C correlation data across 4-, 5-, and even 6-bonds. This expanded NMR data set enabled the elucidation of the palstimolide's planar structure, which is characterized by several 1,5-disposed hydroxy groups as well as a tert-butyl group. The compound showed potent antimalarial activity with an IC50 of 223 nM as well as interesting anti-leishmanial activity with an IC50 of 4.67 µM.

Keywords: antimalarial agents; cyanobacteria; leishmaniosis; macrolide; malaria; natural products.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Structure of palstimolide A (1) together with the related cyanobacterial 40-membered polyhydroxy macrolides bastimolide A [6], amantelides A and B [8], and nuiapolide [9].
Figure 2
Figure 2
Key correlations deduced from COSY/TOCSY (bolded bonds), HMBC data (red arrows), and LR-HSQMBC data (blue arrows) leading to the partial structure of palstimolide A (1). The dashed bond section was assembled from 1D TOCSY data in MeOH-d4, which connected H35 with H31.

References

    1. Burja A.M., Banaigs B., Abou-Mansour E., Grant Burgess J., Wright P.C. Marine cyanobacteria—A prolific source of natural products. Tetrahedron. 2001;57:9347–9377. doi: 10.1016/S0040-4020(01)00931-0. - DOI
    1. Tan L.T. Filamentous tropical marine cyanobacteria: A rich source of natural products for anticancer drug discovery. J. Appl. Phycol. 2010;22:659–676. doi: 10.1007/s10811-010-9506-x. - DOI
    1. Niedermeyer T. Anti-infective Natural Products from Cyanobacteria. Planta Med. 2015;81:1309–1325. doi: 10.1055/s-0035-1546055. - DOI - PubMed
    1. Karpiński T.M. Marine Macrolides with Antibacterial and/or Antifungal Activity. Mar. Drugs. 2019;17:241. doi: 10.3390/md17040241. - DOI - PMC - PubMed
    1. Wang M., Zhang J., He S., Yan X. A Review Study on Macrolides Isolated from Cyanobacteria. Mar. Drugs. 2017;15:126. doi: 10.3390/md15050126. - DOI - PMC - PubMed

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