Antimalarial Bromotyrosine Derivatives from the Australian Marine Sponge <i>Hyattella</i> sp.

Yang, Xinzhou; Davis, Rohan A.; Buchanan, Malcolm S.; Duffy, Sandra; Avery, Vicky M.; Camp, David Brian; Quinn, Ronald J.

doi:10.1021/np900834g

Cited by 61 publications

(94 citation statements)

References 13 publications

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“…Of these, 727 fractions from 154 independent marine biota passed cytotoxicity testing against HEK-293 mammalian cells for evaluation of their selectivity index. A number of the compounds isolated have been published,26,27 whereas others have formed the basis of ongoing projects.…”

Section: Resultsmentioning

confidence: 99%

Development and Optimization of a Novel 384-Well Anti-Malarial Imaging Assay Validated for High-Throughput Screening

Duffy¹,

Avery²

2012

The American Journal of Tropical Medicine and Hygiene

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With the increasing occurrence of drug resistance in the malaria parasite, Plasmodium falciparum, there is a great need for new and novel anti-malarial drugs. We have developed a 384-well, high-throughput imaging assay for the detection of new anti-malarial compounds, which was initially validated by screening a marine natural product library, and subsequently used to screen more than 3 million data points from a variety of compound sources. Founded on another fluorescence-based P. falciparum growth inhibition assay, the DNA-intercalating dye 4′,6-diamidino-2-phenylindole, was used to monitor changes in parasite number. Fluorescent images were acquired on the PerkinElmer Opera High Throughput confocal imaging system and analyzed with a spot detection algorithm using the Acapella data processing software. Further optimization of this assay sought to increase throughput, assay stability, and compatibility with our high-throughput screening equipment platforms. The assay typically yielded Z'-factor values of 0.5–0.6, with signal-to-noise ratios of 12.

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Section: Resultsmentioning

confidence: 99%

Development and Optimization of a Novel 384-Well Anti-Malarial Imaging Assay Validated for High-Throughput Screening

Duffy¹,

Avery²

2012

The American Journal of Tropical Medicine and Hygiene

Self Cite

135

186

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“…10 In a program designed to identify antimalarial drug leads, it was found that psammaplysins F−H exhibited strong antimalarial activity. 8,9 We recently reported the isolation of psammaplysins K−W, together with 19-hydroxyplammaplysins E, P, Q, S, T, U, and W, from an extract of the Balinese sponge Aplysinella strongylata (order Verongida, family Aplysinellidae), with five of these new psammaplysins showing variation in the structural motif attached to C-16 of the aromatic ring, while the remaining compounds contained fatty acid side chains; 19-hydroxypsammaplysin E showed potent antimalarial activity. 11 The relative configuration of psammaplysin A (1) was first determined as (6S*,7S*) in 1985 by single-crystal X-ray crystallographic analysis of its diacetyl derivative (2).…”

mentioning

confidence: 99%

“…11 The relative configuration of psammaplysin A (1) was first determined as (6S*,7S*) in 1985 by single-crystal X-ray crystallographic analysis of its diacetyl derivative (2). 3 Subsequent reports on the relative configuration of psammaplysins C−H were made by comparing their specific rotation values with those of psammaplysin A, 4,8,9,11,12 by chemical shift comparisons, [5][6][7]11 or by ROESY/NOESY correlation data. 8−10 The potent biological activities of the psammaplysins, together with their unusual 1,6-dioxa-2-azaspiro [4.6]undeca-2,7,9-triene motif, clearly justify efforts to resolve their absolute configuration, an aspect of their structure elucidation that could not be pursued in the original X-ray crystallographic work due to inferior crystal quality.…”

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confidence: 99%

Absolute Configuration and Conformational Study of Psammaplysins A and B from the Balinese Marine Sponge Aplysinella strongylata

et al. 2015

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The absolute configuration of psammaplysin A (1) has been assigned as (6R,7R) using experimental and calculated electronic circular dichroism (ECD) data and NMR analysis of MPA esters prepared from the acetamide derivative of 1. Detailed conformational analyses of a truncated model compound of 1 with an in vacuo method and with the PCM solvent model for MeOH have identified the major conformers and factors governing the ECD spectrum of 1. The correlation of the ECD data with the stereochemistry of 1 allows configurational assignment of related psammaplysin analogues on the basis of their ECD spectra.

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“…The H-7 signal appeared at δH 4.99 as an isolated singlet and correlated to an amide carbon atom at δC 159.1 (C-9). These assignments secured the presence of the spirooxepinisoxazoline system in 1 [9]. Furthermore, three mutually coupled methylenes at δH 3.62, 2.13, and 4.07 suggested the presence of a -CH2CH2CH2O-moiety attached to the amide bond of the ) with a strong diagnostic base peak at m/z 122 (C8H8O) arising from a retro Diels-Alder reaction of the carbocyclic ring adjacent to the furan ring [12].…”

Section: Resultsmentioning

confidence: 79%

Bioprospecting of the Balinese marine sponges and nudibranchs

Mudianta

2018

J. Phys.: Conf. Ser.

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Abstract. Secondary metabolites play an invaluable role as a starting point in drug discovery process. Among marine organisms, sponges and nudibranch mollusc (Mollusca: Gastropoda: Nudibranchia) have been the prolific sources of bioactive secondary metabolites with diverse chemical structures and promising bioactivities. This report presents the isolation and structure elucidation of bioactive natural products from the Balinese marine sponge Aplysinella strongylata and the nudibranchs Hypselodoris infucata and Glossodoris hikuerensis. The samples were collected from Tulamben beach Bali, an unexplored site but rich in marine biodiversity. The separation and purification of the metabolites were achieved by mean of NPflash column chromatography and HPLC. Structure elucidations of the isolated compounds were completed by analysis of spectroscopic dataset including 1 H and 2D NMR. A series of bromotyrosine-derived alkaloid possessing a spirooxepinisoxazoline moiety were identified from the extract of A. strongylata. One of the metabolites, 19-hydroxypsammaplysin E (1), showed the best antimalarial activity, with an IC50 value of 6.4 μM. The absolute configuration of psammaplysin series compounds has been assigned as (6R, 7R) using experimental and calculated electronic circular dichroism (ECD) data and NMR analysis of MPA esters prepared from the acetamide derivative of psammaplysin A. A furanosesquiterpen, (-)-furodysinin (2), was identified for the first time from the nudibranch H. infucata. The compound inhibited the growth of HeLa cell line at IC50 102.7 µg/mL. Two new scalarane sesterterpenes (3-4) were characterised from an organic extract of a single specimen of the nudibranch G. hikuerensis.

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Antimalarial Bromotyrosine Derivatives from the Australian Marine Sponge Hyattella sp.

Cited by 61 publications

References 13 publications

Development and Optimization of a Novel 384-Well Anti-Malarial Imaging Assay Validated for High-Throughput Screening

Development and Optimization of a Novel 384-Well Anti-Malarial Imaging Assay Validated for High-Throughput Screening

Absolute Configuration and Conformational Study of Psammaplysins A and B from the Balinese Marine Sponge Aplysinella strongylata

Bioprospecting of the Balinese marine sponges and nudibranchs

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