G Model
CCLET 3568 1–4
4
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The docking model of representative compound 2A and
fungal CYP51 [18] was investigated using the GOLD Suite v5.0
software package (Fig. 3). Like the other triazole compounds, the
4-N of the triazole unit has a van Der Waals interaction with the
heme iron. In addition, we can see that the 5, 6-dihydro-4H-
pyrrolo[3,4-d]thiazol-4-one unit was located in the hydrophobic
pocket composed of Phe-241, Phe-236, Ile-139 and Try-140.
Furthermore, the bromine atom of 2A have a halogen bond with
Ser-382 (not showed), which can explain the potent activities of
2A and 3A.
References
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4. Conclusion
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In summary, a series of novel triazole derivatives containing
g
-lactam were designed and synthesized. Their in vitro antifungal
activities against six pathogenic fungi were evaluated. According
to the results, the R group of the thiazole ring was well tolerated
in vitro. For example, both the pyridyl-substituted compound 3D
and phenyl-substituted compound 3E exhibited good activity
against the Candida spp and Cryptococcus neoformans tested.
However, the activities of these novel triazole derivatives against
Aspergillus fumigatus are moderate and the further studies to
improve activity against Aspergillus fumigatus are ongoing in our
lab. In addition, the cytotoxicities and metabolic properties of
these novel triazole derivatives will be determined in due time.
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Acknowledgment
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This work was supported by the National Natural Science
Foundation of China (No. 21402223).
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Appendix A. Supplementary data
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spanning cytochrome P450 suggests constraints that orient the catalytic domain
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Supplementary data associated with this article can be found,
Please cite this article in press as: Y.-Y. Xu, et al., Design and synthesis of novel triazole derivatives containing
g-lactam as potential