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Identification of Novel Antifungal Skeleton of Hydroxyethyl Naphthalimides with Synergistic Potential for Chemical and Dynamic Treatments

文献类型：期刊论文

作者Zhang, Pengli1,2,3; Tangadanchu, Vijai Kumar Reddy4; Zhou, Chenghe1
刊名MOLECULES
出版日期2022-12-01
卷号27期号:23页码:22
关键词naphthalimide antifungal reactive oxygen species membrane
DOI10.3390/molecules27238453
通讯作者Tangadanchu, Vijai Kumar Reddy(tvijaikumarreddy@wustl.edu) ; Zhou, Chenghe(zhouch@swu.edu.cn)
英文摘要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 mu g/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.
WOS关键词ANTIMICROBIAL ACTIVITY ; BIOLOGICAL EVALUATION ; BIOACTIVE EVALUATION ; DESIGN ; DNA ; DERIVATIVES ; AZOLES ; SERIES
资助项目National Natural Science Foundation of China[SWU-XDZD22007] ; Key Project of Innovation Research[Xm2016039] ; Chongqing Special Foundation for Postdoctoral Research Proposal ; [21971212]
WOS研究方向Biochemistry & Molecular Biology ; Chemistry
语种英语
WOS记录号WOS:000897387400001
出版者MDPI
源URL[http://119.78.100.183/handle/2S10ELR8/304255]  
专题中国科学院上海药物研究所
通讯作者Tangadanchu, Vijai Kumar Reddy; Zhou, Chenghe
作者单位1.Southwest Univ, Inst Bioorgan & Med Chem, Sch Chem & Chem Engn, Key Lab Appl Chem Chongqing Municipal, Chongqing, Peoples R China
2.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan 528400, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Dev Ctr, Shanghai, Peoples R China
4.Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA
推荐引用方式
GB/T 7714		 Zhang, Pengli,Tangadanchu, Vijai Kumar Reddy,Zhou, Chenghe. Identification of Novel Antifungal Skeleton of Hydroxyethyl Naphthalimides with Synergistic Potential for Chemical and Dynamic Treatments[J]. MOLECULES,2022,27(23):22.
APA Zhang, Pengli,Tangadanchu, Vijai Kumar Reddy,&Zhou, Chenghe.(2022).Identification of Novel Antifungal Skeleton of Hydroxyethyl Naphthalimides with Synergistic Potential for Chemical and Dynamic Treatments.MOLECULES,27(23),22.
MLA Zhang, Pengli,et al."Identification of Novel Antifungal Skeleton of Hydroxyethyl Naphthalimides with Synergistic Potential for Chemical and Dynamic Treatments".MOLECULES 27.23(2022):22.

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来源：上海药物研究所

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