Synthesis of naphthalimide triazoles with a novel structuralframework and their anti-<italic>Aspergillus</italic><italic> fumigatus</italic> effects
Pengli Zhang, Jing-Song Lv, Mohammad Fawad Ansari, Narsaiah Battini, Guixin Cai, Cheng‐He Zhou
Abstract
<p indent="0mm">This work designed and exploited a series of unique naphthalimide triazoles as antifungal molecules starting from naphthalic anhydride. The structures of the target compounds were confirmed by spectra. The antifungal activities showed that these naphthalimide triazoles against <italic>A. fumigatus</italic> exhibited superior bioactivities to fluconazole, especially the highly active compound <bold>5j</bold> showed low toxicity to normal cells, no obvious drug resistance and rapid fungicidal potentiality. Further studies revealed that <bold>5j</bold> could not only block the replication of microbial DNA by embedding in DNA to form supramolecular complexes, but also damage the cell membrane and induce ROS generation to affect the survival of fungi. Moreover, <bold>5j</bold> could form a biosupramolecule with sterol 14-α demethylase (CYP51B) of <italic>A. fumigatus</italic> by four hydrogen bonds, and thus affect enzyme function to achieve anti-<italic>A. fumigatus</italic> purpose. These results revealed that these compounds exhibited multifarious antifungal effect. Therefore, this work implied that naphthalimide triazoles with this novel structural framework could be the potential anti-<italic>A. fumigatus</italic> drugs.