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Molecules
2014 Jun 11;196:7869-80. doi: 10.3390/molecules19067869.
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Secondary metabolites from Vietnamese marine invertebrates with activity against Trypanosoma brucei and T. cruzi.
Thao NP
,
No JH
,
Luyen BT
,
Yang G
,
Byun SY
,
Goo J
,
Kim KT
,
Cuong NX
,
Nam NH
,
Van Minh C
,
Schmidt TJ
,
Kang JS
,
Kim YH
.
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Marine-derived natural products from invertebrates comprise an extremely diverse and promising source of the compounds from a wide variety of structural classes. This study describes the discovery of five marine natural products with activity against Trypanosoma species by natural product library screening using whole cell in vitro assays. We investigated the anti-trypanosomal activity of the extracts from the soft corals and echinoderms living in Vietnamese seas. Of the samples screened, the methanolic extracts of several marine organisms exhibited potent activities against cultures of Trypanosoma brucei and T. cruzi (EC50 < 5.0 μg/mL). Among the compounds isolated from these extracts, laevigatol B (1) from Lobophytum crassum and L. laevigatum, (24S)-ergost-4-ene-3-one (2) from Sinularia dissecta, astropectenol A (3) from Astropecten polyacanthus, and cholest-8-ene-3β,5α,6β,7α-tetraol (4) from Diadema savignyi showed inhibitory activity against T. brucei with EC50 values ranging from 1.57 ± 0.14 to 14.6 ± 1.36 μM, relative to the positive control, pentamidine (EC50 = 0.015 ± 0.003 μM). Laevigatol B (1) and 5α-cholest-8(14)-ene-3β,7α-diol (5) exhibited also significant inhibitory effects on T. cruzi. The cytotoxic activity of the pure compounds on mammalian cells was also assessed and found to be insignificant in all cases. This is the first report on the inhibitory effects of marine organisms collected in Vietnamese seas against Trypanosoma species responsible for neglected tropical diseases.
Figure 1. The chemical structures of compounds 1–5.
Figure 2. High throughput screening against T.
brucei growth: (A) Distribution plot of the 861 natural compounds and extracts (blue), 0.5% DMSO (red), and pentamidine at EC100 (black); (B) Frequency distribution of the 861 natural compounds and extracts based on binned normalized activity; (C) Dose response curve of pentamidine against T. brucei, HEK293T, and HepG2 cells.
Figure 3. Inhibitory activity against T. brucei (red) and cytotoxic activity on HEK293T (grey) and HepG2 (black) cells of compounds 1 (A), 2 (B), 3 (C), and 4 (D).
Figure 4. Assessment of the activity of laevigatol B (1) and 5α-cholest-8(14)-ene-3β,7α-diol (5) against intracellular amastigotes of T. cruzi by high content image assay coupled with quantitative image mining algorithm; (A) Images of intracellular T. cruzi with DMSO control (0.5%), compounds 1 and 5 at 50.0 μM; (B) Image analysis of acquired image. Large red dots indicates U2OS nuclei, blue surface refers to cytosol of the corresponding host cell and small red dots refers to T. cruzi nuclei; (C) Quantified cell and parasite numbers from acquired images (4 fields) of control, compounds 1 and 5 treat wells. Scale bar, 40.0 μM.
Dimitri,
R&D investments for neglected diseases can be sensitive to the economic goal of pharmaceutical companies.
2012, Pubmed
Dimitri,
R&D investments for neglected diseases can be sensitive to the economic goal of pharmaceutical companies.
2012,
Pubmed
Fèvre,
The burden of human African trypanosomiasis.
2008,
Pubmed
Ma,
Norselic acids A-E, highly oxidized anti-infective steroids that deter mesograzer predation, from the Antarctic sponge Crella sp.
2009,
Pubmed
Molinski,
Drug development from marine natural products.
2009,
Pubmed
Quang,
Cytotoxic and anti-inflammatory cembranoids from the Vietnamese soft coral Lobophytum laevigatum.
2011,
Pubmed
Regalado,
Antiprotozoal steroidal saponins from the marine sponge Pandaros acanthifolium.
2010,
Pubmed
Sanchez,
Examination of the mode of action of the almiramide family of natural products against the kinetoplastid parasite Trypanosoma brucei.
2013,
Pubmed
Schmidt,
Complete structural assignment of serratol, a cembrane-type diterpene from Boswellia serrata, and evaluation of its antiprotozoal activity.
2011,
Pubmed
Schmidt,
The potential of secondary metabolites from plants as drugs or leads against protozoan neglected diseases - part II.
2012,
Pubmed
Schmidt,
The potential of secondary metabolites from plants as drugs or leads against protozoan neglected diseases - part I.
2012,
Pubmed
Siqueira-Neto,
An image-based high-content screening assay for compounds targeting intracellular Leishmania donovani amastigotes in human macrophages.
2012,
Pubmed
Thao,
Steroidal constituents from the starfish Astropecten polyacanthus and their anticancer effects.
2013,
Pubmed
,
Echinobase
Watts,
The structural diversity and promise of antiparasitic marine invertebrate-derived small molecules.
2010,
Pubmed
Zofou,
Bioactive natural products derived from the Central African flora against neglected tropical diseases and HIV.
2013,
Pubmed
