| Autor: |
Zhang P; Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China.; Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528400, China.; Drug Discovery and Development Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China., Tangadanchu VKR; Department of Radiology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA., Zhou C; Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China. |
| Jazyk: |
angličtina |
| Zdroj: |
Molecules (Basel, Switzerland) [Molecules] 2022 Dec 02; Vol. 27 (23). Date of Electronic Publication: 2022 Dec 02. |
| DOI: |
10.3390/molecules27238453 |
| Abstrakt: |
The invasion of pathogenic fungi poses nonnegligible threats to the human health and agricultural industry. This work exploited a family of hydroxyethyl naphthalimides as novel antifungal species with synergistic potential of chemical and dynamic treatment to combat the fungal resistance. These prepared naphthalimides showed better antifungal potency than fluconazole towards some tested fungi including Aspergillus fumigatus , Candida tropicalis and Candida parapsilosis 22019. Especially, thioether benzimidazole derivative 7f with excellent anti- Candida tropicalis efficacy (MIC = 4 μg/mL) possessed low cytotoxicity, safe hemolysis level and less susceptibility to induce resistance. Biochemical interactions displayed that 7f could form a supramolecular complex with DNA to block DNA replication, and constitute a biosupermolecule with cytochrome P450 reductase (CPR) from Candida tropicalis to hinder CPR biological function. Additionally, 7f presented strong lipase affinity, which facilitated its permeation into cell membrane. Moreover, 7f with dynamic antifungal potency promoted the production and accumulation of reactive oxygen species (ROS) in cells, which destroyed the antioxidant defence system, led to oxidative stress with lipid peroxidation, loss of glutathione, membrane dysfunction and metabolic inactivation, and eventually caused cell death. The chemical and dynamic antifungal synergistic effect initiated by hydroxyethyl naphthalimides was a reasonable treatment window for prospective development. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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