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the unsubstituted derivative 8a. Interestingly, 3,4-dimentyl deriva-
tive 8j and 3,5-dimentyl derivative 8l are more active against
C. tropicalis and C. parapsilosis than compound 8a.
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In summary, structure-based drug design was used to discover new
antifungal azoles with phenylacetamide side chain. In vitro antifun-
gal activity assay indicated that the new azoles showed moderate-
to-good activity against invasive fungal pathogens. Compound 8h
showed the best inhibitory against C. albicans and C. neoformans
(MIC = 0.0156 lg ⁄ mL). Molecular docking studies revealed that it
interacted with CACYP51 mainly through hydrophobic and van der
Waals interactions. Because the phenylacetamide represents a new
type of side chain in azole antifungal agents, further structural mod-
ification is essential to obtain more information about SAR.
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Acknowledgment
This work was supported by the National Natural Science Founda-
tion of China (Grant Nos. 30930107), Shanghai Rising-Star Program
(Grant Nos. 09QA1407000), Science and Technology Commission of
Shanghai (Grant Nos. 10431902100) and Shanghai Leading Aca-
demic Discipline Project (Project Nos. B906).
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antifungal dioxane-triazole derivatives: synthesis and in vitro
activities. Bioorg Med Chem Lett;19:2013–2017.
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