Fusaricide, a New Cytotoxic <i>N</i>-Hydroxypyridone from <i>Fusarium </i>sp.

Mcbrien, Kimberly D.; Gao, Qi; Huang, Stella; Klohr, Steven E.; Wang, Richard R.; Pirnik, Dolores M.; Neddermann, Kim M.; Bursuker, Isia; Kadow, Kathleen F.; Leet, John E.

doi:10.1021/np960521t

Cited by 54 publications

(30 citation statements)

References 15 publications

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“…18 Furthermore, many of these alkaloids exhibit cancer cell growth-inhibitory activity and are investigated as potential anticancer agents. Examples include cytotoxic fusaricide (1) 19 and melicobisquinolinone B (2, Figure 1). 20 In addition, zanthosimuline (3) is active against multidrug resistant KB-VI cancer cells, while huajiaosimuline (4) exhibits a selective cytotoxicity profile showing the greatest activity with estrogen receptor-positive ZR-75-1 breast cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Structural Simplification of Bioactive Natural Products with Multicomponent Synthesis. 2. Antiproliferative and Antitubulin Activities of Pyrano[3,2-c]pyridones and Pyrano[3,2-c]quinolones

et al. 2008

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Pyrano[3,2-c]pyridone and pyrano[3,2-c]quinolone structural motifs are commonly found in alkaloids manifesting diverse biological activities. As part of a program aimed at structural simplification of bioactive natural products utilizing multicomponent synthetic processes, we developed compound libraries based on these privileged heterocyclic scaffolds. The selected library members display low nanomolar antiproliferative activity and induce apoptosis in human cancer cell lines. Mechanistic studies reveal that these compounds induce cell cycle arrest in the G2/M phase and block in vitro tubulin polymerization. Because of the successful clinical use of microtubule-targeting agents, these heterocyclic libraries are expected to provide promising new leads in anticancer drug design.

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Section: Introductionmentioning

confidence: 99%

Structural Simplification of Bioactive Natural Products with Multicomponent Synthesis. 2. Antiproliferative and Antitubulin Activities of Pyrano[3,2-c]pyridones and Pyrano[3,2-c]quinolones

et al. 2008

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“…The 1 H- 1 H COSY spectrum of 1 indicated three spin systems: C5–C6, C7–C8(-C18)–C9–C10(-C17)–C11, and C13–C15, which were also verified by the corresponding HMBC correlations ( Figure 3 ). Meanwhile, the HMBC correlations from the methyl group CH 3 -16 to C-7, C-11, C-12 and C-13, and from H-7 to C-2 (δ C 159.4), C-3 (δ C 114.6), and C-4 (δ C 165.8), as well as a correlation from H-13 to the oxygenated olefinic carbon C-4, suggested that compound 1 should be an analog of fusaricide [ 25 , 26 ]. However, one oxygenated methine (instead of a methylene) at 11-position and one methoxy group at 1-position were observed in 1 .…”

Section: Resultsmentioning

confidence: 99%

“…The absolute configuration of compound 1 was determined by comparing its optical rotation with those of ( 3 ) [ 28 ], cordypyridone C ( 6 ) [ 27 ], 14-hydroxycordypyridone C ( 7 ) [ 27 ] and fusaricide ( 8 ) [ 25 , 26 , 27 ], and its CD with that of compound 3 . The absolute configuration of the p -bromobenzoate of compound 7 was established using anomalous scattering X-ray crystallographic methods [ 27 ].…”

Section: Resultsmentioning

confidence: 99%

A New N-methoxypyridone from the Co-Cultivation of Hawaiian Endophytic Fungi Camporesia sambuci FT1061 and Epicoccum sorghinum FT1062

Sarotti

Yang

et al. 2017

Molecules

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A new N-methoxypyridone analog (1), together with four known compounds, was isolated from the co-culture of Hawaiian endophytic fungi Camporesia sambuci FT1061 and Epicoccum sorghinum FT1062. The structure of the new compound was elucidated as 11S-hydroxy-1-methoxyfusaricide (1) by extensive spectroscopic analysis and comparison with the literature. The absolute configuration of 1 was determined by comparison with the experimental and calculated ECD spectra. The absolute configuration of compound 3 was investigated and renamed as (+)-epipyridone by comparison of the optical rotation and CD spectrum with those of 1. The other known compounds were identified as epicoccarine B (2), D8646-2-6 (4), and iso-D8646-2-6 (5). Compounds 4 and 5 showed modest inhibitory activity towards pathogenic fungi. Epicoccarine B (2) inhibited A2780 and TK-10 with an IC50 value of 22 μM.

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“…It was pre‐established that proinflammatory cytokines like TNF‐α and interleukin‐6 (IL‐6) become attractive targets for adjuvant treatment of cancer as they are master regulators of tumor‐related inflammation and tumorigenesis (Grivennikov & Karin, ). As per showed in Figure , alkaloids with pyrano[3,2‐c]pyridone and pyrano[3,2‐c]quinolone like fusaricide (1, Figure ) (McBrien et al., ), melicobisquinolinone‐B (2, Figure ) (Kamperdick, Van, Van Sung, & Adam, ), zanthosimuline (3, Figure ), and huajiaosimuline (4, Figure ) (Chen et al., ) referred as potential anticancer agents. Additionally, Quinolactin‐A (Sasaki et al., ) (5, Figure )—a 4‐quinolone alkaloid, isolated from the cultured broth of Penicillium sp.…”

Section: Introductionmentioning

confidence: 99%

Evaluation and in vivo efficacy study of pyrano[3,2‐c]quinoline analogues as TNF‐α inhibitors

et al. 2019

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A series of pyrano[3,2 c]quinoline was evaluated for its in vivo efficacy as TNF‐α inhibitor using LPS, phosphodiesterase (PDE)‐4, and CIA assays in different mice/rat models. The synthesis was performed using one‐pot multicomponent condensation between 2,4‐dihydroxy‐1‐methylquinoline, malononitrile, and diverse un(substituted) aromatic aldehydes. In vivo efficacy of the title compounds was evaluated using LPS assay in BALB/c mice, PDE4 inhibition in ketamine–xylazine‐induced anesthetize SD rats, and CIA assay was performed in DBA/1J mice as per the standard literature protocols. The outcome of the study revealed that compound 4v was found to be most promising candidate of the series. It was efficacious with 48.8 ± 13.0% inhibition of TNF‐α release at 100 mg/kg p.o., in the LPS assay in Balb/c mice model. It was effective in PDE4 assay in ketamine–xylazine‐induced anesthetize SD rats with duration of 38.3 ± 4.5 min for reversal of anesthetic effect and also showed significant inhibition of PDE4 in salbutamol treated U937 cell assay. It was also abolished TNF‐α induced phosphorylation and degradation of IκBα. Ultimately, its effect on CIA‐related bone and cartilage damage was found statistically similar to Enbrel.

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Fusaricide, a New Cytotoxic N-Hydroxypyridone from Fusarium sp.

Abstract: A new cytotoxic N-hydroxypyridone, fusaricide (1), was isolated from a Fusarium sp. Its structure was solved by X-ray diffraction and spectroscopic analyses.

Cited by 54 publications

References 15 publications

Structural Simplification of Bioactive Natural Products with Multicomponent Synthesis. 2. Antiproliferative and Antitubulin Activities of Pyrano[3,2-c]pyridones and Pyrano[3,2-c]quinolones

Structural Simplification of Bioactive Natural Products with Multicomponent Synthesis. 2. Antiproliferative and Antitubulin Activities of Pyrano[3,2-c]pyridones and Pyrano[3,2-c]quinolones

A New N-methoxypyridone from the Co-Cultivation of Hawaiian Endophytic Fungi Camporesia sambuci FT1061 and Epicoccum sorghinum FT1062

Evaluation and in vivo efficacy study of pyrano[3,2‐c]quinoline analogues as TNF‐α inhibitors

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