Mechanism of Inhibition of Eukaryotic Protein Synthesis by Trichothecene Fungal Toxins

Cundliffe, Eric; Cannon, Michael; Davies, Julian

doi:10.1073/pnas.71.1.30

Cited by 204 publications

(126 citation statements)

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“…3,15-didesacetylcalonectrin). Thus esterification of the hydroxyl at R3 appears to induce an increased I-type response, in agreement with the work of Cundliffe et al (1974), where it was suggested that the presence of an oxygen-containing substituent at R3 is necessary to produce such an effect.…”

Section: Discussionsupporting

confidence: 88%

“…4e), and the 'run off' was complete when the concentration of diacetoxyscirpenol was lowered further (1-10g/ml). Total 'run off' was also achieved by adding 15-acetoxyscirpendiol at 1-5,ug/ml, or T-2 toxin, observed by Cundliffe et al (1974) to be an I-type inhibitor (Schindler, 1974), at any concentration between 1 and 150jug/ml (Fig. 4h).…”

Section: Resultsmentioning

confidence: 99%

“…Thus with trichodermin a concentration-dependent overlap of effects can occur and a true E-type response is observed only at high concentrations of the drug. The possibility exists, therefore, that a similar overlap might be observed with a drug originally shown to give an I-type response (Cundliffe et al, 1974;Schindler, 1974) so that at most drug concentrations total polyribosome disaggregation is observed, whereas high drug concentrations may partially or even totally stabilize polyribosome profiles.…”

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confidence: 89%

“…However, the 12,13-epoxytrichothecenes do not appear to share a common mode of action when added to systems in vivo or in vitro containing polyribosomes, and on this basis they have been divided into two subgroups (Schindler, 1974). One subgroup, including trichodermin, stabilizes polyribosome profiles (E-type response), an effect that is consistent with inhibition of elongation (Cundliffe et al, 1974). A similar stabilization would be observed if termination of nascent peptide chains was inhibited (Wei et al, 1974b).…”

mentioning

confidence: 99%

“…A similar stabilization would be observed if termination of nascent peptide chains was inhibited (Wei et al, 1974b). The other subgroup, including T-2 toxin and diacetoxyscirpenol, causes rapid disaggregation of polyribosomes (I-type response), suggesting that the compounds affect either some stage in the initiation of protein synthesis (Cundliffe et al, 1974) or at least are capable of binding only to recently initiated ribosomes (Cannon et al, 1976a). Carter et al (1976) have claimed that trichodermin, although previously shown to give an E-type response (Cundliffe et al, 1974), affects polyribosome profiles differently depending on the concentration of drug added.…”

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confidence: 99%

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Structural requirements for the inhibitory action of 12,13-epoxytrichothecenes on protein synthesis in eukaryotes

Carter

Cannon

1977

Biochemical Journal

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1. The inhibitory actions of ten trichothecene antibiotics were investigated, in reticulocyte cell-free systems synthesizing protein in vitro, by studying polyribosome profiles and kinetics of amino acid incorporation in the presence or absence of the drugs. 2. The modes of action observed were critically dependent on the drug concentrations used, but the antibiotics tested could be divided into four distinct groups, each exerting a characteristic inhibitory response. 3. The inhibitory action observed in every case was controlled by the chemical structure of the individual trichothecene and in particular was closely related to the nature of the substituent groups present on C-3, C-4, C-8 and C-15 of the molecule.

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Section: Discussionsupporting

confidence: 88%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 89%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Structural requirements for the inhibitory action of 12,13-epoxytrichothecenes on protein synthesis in eukaryotes

Carter

Cannon

1977

Biochemical Journal

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Phytotoxicity of selected trichothecenes usingChlamydomonas reinhardtii as a model system

1999

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Trichothecenes are potent inhibitors of cytoplasmic protein synthesis which can affect the severity of plant diseases such as wheat head scab. While many trichothecene-producing fungi share the initial biosynthetic intermediates, Fusarium sp. are unique in the production of trichothecenes containing an oxygen function at C-3. Although the initial trichothecene and the final products have a C-3 hydroxyl group, the intermediate steps are acetylated at C-3. By using Chlamydomonas reinhardtii, a unicellular plant with a well-defined genetic system, we were able to test the proposal that trichothecenes with a C-3 hydroxyl are more toxic to plants, as well as demonstrate that C. reinhardtii is a promising plant trichothecene bioassay system. Seven pairs of trichothecenes with either a C-3 hydroxyl or C-3 acetyl group were assayed. Our results confirm that trichothecenes acetylated at C-3 were far less toxic to Chlamydomonas than those with a C-3 hydroxyl group.

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Synthesis and Antifungal Activities of Trichodermin Derivatives as Fungicides on Rice

Cheng

Zhou

et al. 2013

Chemistry & Biodiversity

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Twenty new trichodermin derivatives, 2a-5, containing alkoxy, acyloxy, and Br groups in 4-, 8-, 9-, 10- and 16-positions were synthesized and characterized. The antifungal activities of the new compounds against rice false smut (Ustilaginoidea virens), rice sheath blight (Rhizoctonia solani), and rice blast (Magnaporthe grisea) were evaluated. The results of bioassays indicated that the antifungal activities were particularly susceptible to changes at 4-, 8-, and 16-positions, but low to changes at 9- and 10-positions. Most of these target compounds exhibited good antifungal activities at the concentration of 50 mg l(-1) . Compound 4 (9-formyltrichodermin; EC50 0.80 mg l(-1) ) with an CHO group at 9-position displayed nearly the same level of antifungal activity against Ustilaginoidea virens as the commercial fungicide prochloraz (EC50 0.82 mg l(-1) ), while compound 3f ((8R)-8-{[(E)-3-phenylprop-2-enoyl]oxy}trichodermin; EC50 3.58 and 0.74 mg l(-1) ) with a cinnamyloxy group at C(8) exhibited much higher antifungal activities against Rhizoctonia solani and Magnaporthe grisea than the commercial fungicides prochloraz (EC50 0.96 mg l(-1) ) and propiconazole (EC50 5.92 mg l(-1) ), respectively. These data reveal that compounds 3f and 4 possess high antifungal activities and may serve as lead compounds for the development of fungicides in the future.

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Mechanism of Inhibition of Eukaryotic Protein Synthesis by Trichothecene Fungal Toxins

Abstract: The 12,13-epoxytrichothecenes, a group of sesquiterpenoid fungal antibiotics, inhibit protein syn-

Cited by 204 publications

References 12 publications

Structural requirements for the inhibitory action of 12,13-epoxytrichothecenes on protein synthesis in eukaryotes

Structural requirements for the inhibitory action of 12,13-epoxytrichothecenes on protein synthesis in eukaryotes

Phytotoxicity of selected trichothecenes usingChlamydomonas reinhardtii as a model system

Synthesis and Antifungal Activities of Trichodermin Derivatives as Fungicides on Rice

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