Emerging antifungal azoles and effects on Magnaporthe grisea.
Derivatives of pyrazolo[1,5-a][1, 3, 5]triazine-2,4-dione,pyrazolo[1,5-c][1, 3, 5]thiadiazine-2-one, pyrazolo[3,4-d][1, 3]thiazine-4-one, and pyrazolo[3,4-d][1, 3]thiazine-4-thione were screened for antifungal activity against the causal agent of rice blast disease, Magnaporthe grisea. The compounds were tested at doses ranging from 10 to 200mugml(-1), using the commercial fungicide tricyclazole as reference compound. All triazine derivatives inhibited the growth and pigmentation of the mycelia less effectively than tricyclazole. The thiadiazine derivatives proved to be more effective than their triazine counterparts, but only 4-(butylimino)-7-methylpyrazolo[1,5-c][1,3,5]thiadiazine-2-one (2h) and 4-(cyclohexylimino)-7-methylpyrazolo[1,5-c][1,3,5]thiadiazine-2-one (2j) were more effective than tricyclazole. Pyrazolo[3,4-d][1,3]thiazine-4-one derivatives were active only at the highest doses, whereas members of the pyrazolo[3,4-d][1,3]thiazine-4-thione series inhibited fungal growth at the lowest concentrations used, at which tricyclazole had no effect. A dose-dependent mechanism might be responsible for this effect, with lipophilicity as the governing factor. Within a given set, the presence of a cyclohexyl or an n-butyl group generally increased antifungal activity, with respect to both growth inhibition and cell de-pigmentation of the mycelium, suggesting that a higher lipophilicity might improve transport inside the cells. SEM and TEM of M. grisea hyphae showed that treatment with the most active substance (2h) caused significant ultrastructural effects, particularly on the endomembrane system, suggesting a mechanism of action similar to that of most azole fungicides. Dissimilarities were also observed, with no alterations of the cell wall evident. In conclusion, several compounds showed greater inhibition than tricyclazole, and therefore provide useful new chemistry for control of M. grisea infections.
Mares
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Dipartimento delle Risorse Naturali e Culturali, Università degli Studi di Ferrara, V. Ercole l D'Este 32, Ferrara, Italy. mrd@unife.it
Romagnoli
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C
Andreotti
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E
Forlani
G
G
Guccione
S
S
Vicentini
C B
CB
D000935:Antifungal Agents / Q000494:pharmacology*; D001393:Azoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D003470:Culture Media; D020082:Magnaporthe / Q000187:drug effects* / Q000254:growth & development / Q000648:ultrastructure; D008826:Microbial Sensitivity Tests / Q000379:methods; D008855:Microscopy, Electron, Scanning; D012275:Oryza / Q000382:microbiology; D010935:Plant Diseases / Q000382:microbiology; D011720:Pyrazoles / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
D000935:Antifungal Agents; D001393:Azoles; D003470:Culture Media; D011720:Pyrazoles; D013844:Thiazoles; C041191:tricyclazole