Entonalactams A–C: Isoindolinone derivatives from an Australian rainforest fungus belonging to the genus Entonaema

Choomuenwai, Vanida; Beattie, Karren D.; Healy, Peter Conrad; Andrews, Katherine Thea; Fechner, Nigel; Davis, Rohan A.

doi:10.1016/j.phytochem.2015.05.018

Cited by 25 publications

(31 citation statements)

References 39 publications

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“…Furthermore, the 13 C NMR spectrum showed an amide and carboxyl carbon at δ C 166.8 (C-1) and 170.7 (C-2′), 12 aromatic carbons at δ C 98.6 (C-6), 101.8 (C-4), 109.5 (C-7a), 112.0 (C-11), 117.5 (C-13), 123.7 (C-8), 128.2 (C-12), 142.5 (C-9), 147.7 (C-10), 151.4 (C-3a), 157.9 (C-7), and 162.6 (C-5), one methine carbon at δ C 56.4 (C-3), one methyl carbon at δ C 20.7 (C-12-CH 3 ), two methoxy carbons at δ C 55.3 (C-7-OCH 3 ) and 55.7 (C-10-OCH 3 ), and one methylene carbon at δ C 41.8 (C-1′) (Table ). These spectroscopic data for 1 were similar to that of the known isoindolinone compounds daldinan A ( 8 ) and entonalactam A ( 9 ) . Therefore, 1 might have the 5-hydroxy-7-methoxyisoindolinone skeleton with a 2-hydroxy-3-methoxy-5-methylphenyl group at C-3.…”

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confidence: 71%

Isoindolinones, Phthalides, and a Naphthoquinone from the Fruiting Body of Daldinia concentrica

et al. 2018

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A chemical investigation of the ascomycetes of Daldinia concentrica was performed using silica gel column chromatography, ODS column chromatography, and preparative HPLC. Two new isoindolinone compounds, daldinans B (1) and C (2), two new phthalide compounds, daldinolides A (3) and B (4), and a new naphthoquinone, daldiquinone (5), were isolated together with two known compounds (6 and 7). The structures of 1, 2, and 5 were established using NMR, MS, and IR methods, and the structures of 3 and 4 were determined by derivatization from known compounds (6 and 7). 5 exhibited antiangiogenesis activity against HUVECs (IC = 7.5 μM).

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confidence: 71%

Isoindolinones, Phthalides, and a Naphthoquinone from the Fruiting Body of Daldinia concentrica

et al. 2018

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“…Australia has a high level of biodiversity providing an exceptional resource for natural product drug discovery. We have previously reported the identification and biological profiling of compounds originating from plants [ 32 ], marine invertebrates [ 33 , 34 , 35 ] and fungi [ 36 ], which possess anti-parasitic activity.…”

Section: Introductionmentioning

confidence: 99%

Screening a Natural Product-Based Library against Kinetoplastid Parasites

et al. 2017

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Kinetoplastid parasites cause vector-borne parasitic diseases including leishmaniasis, human African trypanosomiasis (HAT) and Chagas disease. These Neglected Tropical Diseases (NTDs) impact on some of the world’s lowest socioeconomic communities. Current treatments for these diseases cause severe toxicity and have limited efficacy, highlighting the need to identify new treatments. In this study, the Davis open access natural product-based library was screened against kinetoplastids (Leishmania donovani DD8, Trypanosoma brucei brucei and Trypanosoma cruzi) using phenotypic assays. The aim of this study was to identify hit compounds, with a focus on improved efficacy, selectivity and potential to target several kinetoplastid parasites. The IC50 values of the natural products were obtained for L. donovani DD8, T. b. brucei and T. cruzi in addition to cytotoxicity against the mammalian cell lines, HEK-293, 3T3 and THP-1 cell lines were determined to ascertain parasite selectivity. Thirty-one compounds were identified with IC50 values of ≤10 µM against the kinetoplastid parasites tested. Lissoclinotoxin E (1) was the only compound identified with activity across all three investigated parasites, exhibiting IC50 values <5 µM. In this study, natural products with the potential to be new chemical starting points for drug discovery efforts for kinetoplastid diseases were identified.

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“…Compounds 1 – 13 have been recently added to the Davis open-access natural product-based library, which is curated by Compounds Australia, Griffith University. Currently this library consists of 512 distinct structures, the majority of which have been obtained from Australian natural sources, such as endophytic fungi, plants, macrofungi, and marine invertebrates …”

Section: Resultsmentioning

confidence: 99%

“…Therefore, the structure of compound 12 was also confirmed by X-ray crystallography (Figure 3 Compounds Australia, Griffith University. Currently this library consists of 512 distinct structures, the majority of which have been obtained from Australian natural sources, such as endophytic fungi, 28 plants, 29 macrofungi, 30 and marine invertebrates. 31 To date all the gibberellic acid semisynthesized analogues (2−13) together with the NP scaffold (1) have been evaluated for their cytotoxicity against a human prostate cancer cell line, LNCaP (lymph node metastasis, androgen-sensitive), using a metabolic assay (alamarBlue).…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Identification of Gibberellic Acid Derivatives That Deregulate Cholesterol Metabolism in Prostate Cancer Cells

et al. 2018

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The naturally occurring pentacyclic diterpenoid gibberellic acid (1) was used in the generation of a drug-like amide library using parallel-solution-phase synthesis. Prior to the synthesis, a virtual library was generated and prioritized based on drug-like physicochemical parameters such as log P, hydrogen bond donor/acceptor counts, and molecular weight. The structures of the synthesized analogues (2-13) were elucidated following analysis of the NMR, MS, UV, and IR data. Compound 12 afforded crystalline material, and its structure was confirmed by X-ray crystallographic analysis. All compounds were evaluated in vitro for cytotoxicity and deregulation of lipid metabolism in LNCaP prostate cancer cells. While no cytotoxic activity was identified at the concentrations tested, synthesized analogues 3, 5, 7, 10, and 11 substantially reduced cellular uptake of free cholesterol in prostate cancer cells, suggesting a novel role of gibberellic acid derivatives in deregulating cholesterol metabolism.

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Entonalactams A–C: Isoindolinone derivatives from an Australian rainforest fungus belonging to the genus Entonaema

Cited by 25 publications

References 39 publications

Isoindolinones, Phthalides, and a Naphthoquinone from the Fruiting Body of Daldinia concentrica

Isoindolinones, Phthalides, and a Naphthoquinone from the Fruiting Body of Daldinia concentrica

Screening a Natural Product-Based Library against Kinetoplastid Parasites

Identification of Gibberellic Acid Derivatives That Deregulate Cholesterol Metabolism in Prostate Cancer Cells

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