Isolation and characterization of spliceostatin B, a new analogue of FR901464, from Pseudomonas sp. No. 2663

Li, Xiangyang; Biswas, Sreya; Tang, Gong‐Li; C, Yi

doi:10.1038/ja.2013.38

Cited by 19 publications

(29 citation statements)

References 10 publications

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“…Corroborating this observation, a recent report provides evidence that changing the epoxide of FD-985 to a cyclopropane does not drastically alter its cytotoxicity but instead appears to stabilize the compound (29). Furthermore, recent papers identified an analog of FR901464, termed spliceostatin B, and two members of the thailanstatin family of natural products that resemble FR901464 and that do not contain the epoxide (35,36). All three compounds are considerably less cytotoxic than their epoxide-containing counterparts.…”

Section: Discussionmentioning

confidence: 89%

Coherence between Cellular Responses and in Vitro Splicing Inhibition for the Anti-tumor Drug Pladienolide B and Its Analogs

Effenberger

Anderson

Bray

et al. 2014

Journal of Biological Chemistry

104

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Background: Pladienolide B is a complex natural product that potently inhibits pre-mRNA splicing. Results: The same molecular features of pladienolide B are required for the drug's effects on cell growth, morphology, and splicing. Conclusion: Simplified synthesis and modification of active pladienolide B is possible. Significance: Pladienolide B analogs can be used to study the relationship between splicing and cancer cell function.

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Section: Discussionmentioning

confidence: 89%

Coherence between Cellular Responses and in Vitro Splicing Inhibition for the Anti-tumor Drug Pladienolide B and Its Analogs

Effenberger

Anderson

Bray

et al. 2014

Journal of Biological Chemistry

104

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“…Although 3 belongs to the same family of compounds as 4 and 5, the name thailanstatin A was used when reporting compound 3, as it had been isolated from a Burkholderia thailandensis-like strain. It has recently been shown that strain FERM BP-3421 produces carboxylic acids 1, 2, and 3 in addition to hemiketals 4 and 5 (22,25), whereas only 3 and two chlorohydrin adducts of 3 have been isolated from MSMB 43 (20). We chose to use the term spliceostatin in this manuscript to refer to all congeners 1-5…”

mentioning

confidence: 99%

Spliceostatin hemiketal biosynthesis in Burkholderia spp. is catalyzed by an iron/α-ketoglutarate–dependent dioxygenase

Eustáquio

Janso

Ratnayake

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Significance Spliceostatins are bacterial natural products that show promising anticancer activity. Understanding how the bacterium makes spliceostatins will aid efforts toward a sustainable route for their production. Moreover, altering the chemical structure of a natural product is usually necessary to improve its pharmaceutical properties. For example, the parent spliceostatin molecule contains an unstable hemiketal chemical group. Contrary to previous hypotheses, we report on the identification of a dioxygenase enzyme responsible for hemiketal biosynthesis. Deletion of the corresponding dioxygenase gene led to a strain that produces exclusively spliceostatin congeners that are more stable than, and as active as, the parent compound, when derivatized to increase cell permeability. The strain generated in this study will be the basis for future development.

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“…Since three carbonyl groups and three double bonds accounted for six degrees of unsaturation, the remaining unsaturation were assumed for the presence of a tricyclic ring system in 1 . The data mentioned above indicated that 1 was a spliceostatin analog . Comparison of the NMR data of 1 with those of 3 indicated the major difference between 1 and 3 was the tetrahydropyran moiety (ring A in 3 ).…”

Section: Resultsmentioning

confidence: 95%

“…The spliceostatins, a group of peptide/polyketide hybrid natural products, [1 -3] were structurally characterized by two poly-substituted tetrahydropyran rings connected by a diene chain. [4][5][6][7][8][9][10] These metabolites displayed potent cytotoxic properties in human cancer cell lines targeting the alternative splicing process. These natural products could inhibit the spliceosome, a key protein complex acting in pre-mRNA splicing.…”

Section: Introductionmentioning

confidence: 99%

Cytotoxic Spliceostatin Analogs from Pseudomonas sp.

Zhao

Zhang

et al. 2019

Chemistry & Biodiversity

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Two new spliceostatin analogs, designed as spliceostatins J and K (1 and 2), were isolated and identified from the culture of Pseudomonas sp., along with two known ones, FR901464 (3) and spliceostatin E (4). Their structures were elucidated by detailed interpretation of their spectroscopic data, especially 2D‐NMR and HR‐ESI‐MS. Spliceostatin J (1) represented the first example of spliceostatins bearing an unusual hexahydrofuro[3,4‐b]furan moiety. Biological assay showed all the isolated compounds except 1 displayed potent cytotoxic activities against two cancer cell lines (MDA‐MB‐231 and A‐549). Structure‐activity‐relationship studies revealed that the tetrahydropyran ring in spliceostatin analogs was necessary for their bioactive retention.

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Isolation and characterization of spliceostatin B, a new analogue of FR901464, from Pseudomonas sp. No. 2663

Cited by 19 publications

References 10 publications

Coherence between Cellular Responses and in Vitro Splicing Inhibition for the Anti-tumor Drug Pladienolide B and Its Analogs

Coherence between Cellular Responses and in Vitro Splicing Inhibition for the Anti-tumor Drug Pladienolide B and Its Analogs

Spliceostatin hemiketal biosynthesis in Burkholderia spp. is catalyzed by an iron/α-ketoglutarate–dependent dioxygenase

Cytotoxic Spliceostatin Analogs from Pseudomonas sp.

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