Design, synthesis and evaluation of biphenyl imidazole analogues as potent antifungal agents
| Autor: | Mengya Wu, Maosheng Cheng, Xin Su, Bin Sun, Peng Wei, Liyu Zhao, Shizhen Zhao, Xiangqian Zhang, Dongmei Zhao |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Antifungal Agents
Cell Survival Itraconazole Clinical Biochemistry Pharmaceutical Science Microbial Sensitivity Tests 01 natural sciences Biochemistry Fungal Proteins Candida tropicalis Structure-Activity Relationship chemistry.chemical_compound Cytochrome P-450 Enzyme System Catalytic Domain Cell Line Tumor Candida albicans Drug Discovery medicine Humans Protein Isoforms Structure–activity relationship Imidazole Fluconazole Molecular Biology Binding Sites biology 010405 organic chemistry Chemistry Aspergillus fumigatus Biphenyl Compounds Organic Chemistry Imidazoles biology.organism_classification Corpus albicans 0104 chemical sciences Molecular Docking Simulation 010404 medicinal & biomolecular chemistry Drug Design Molecular Medicine Lead compound medicine.drug |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 29:2448-2451 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2019.07.037 |
| Popis: | To further explore the structure activity relationships (SARs) of our previously discovered antifungal lead compound (1), a series of biphenyl imidazole analogues were designed, synthesized and evaluated for their in vitro antifungal activity. Many of the synthesized compounds showed excellent activity against Candida albicans and Candida tropicalis. Among these compounds, 2-F substituted analogue 12m displayed the most remarkable in vitro activity against C. albicans, C. neoformans, A. fumigatus and fluconazole-resistant C. alb. strains, which is superior or comparable to the activity of the reference drugs fluconazole and itraconazole. Notably, the compound 12m exhibited low inhibition profiles for various human cytochrome P450 isoforms and showed low toxicity to mammalian A549 cells and U87 cells. The SARs and binding mode established in this study will be useful for further lead optimization. |
| Databáze: | OpenAIRE |
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