灰葡萄孢菌
尖孢镰刀菌
交替链格孢
生物
镰刀菌
烟曲霉
病原真菌
孢子萌发
微生物学
真菌
植物
孢子
作者
Lyudmyla Antypenko,Zhanar Sadykova,Kostiantyn Shabelnyk,Fatuma Meyer,С. И. Коваленко,Vera Meyer,Leif‐Alexander Garbe,Karl Steffens
标识
DOI:10.1002/ardp.201900092
摘要
Abstract Due to their high specificity and efficacy, triazoles have become versatile antifungals to treat fungal infections in human healthcare and to control phytopathogenic fungi in agriculture. However, azole resistance is an emerging problem affecting human health as well as food security. Here we describe the synthesis of 10 novel {2‐(3‐R‐1 H ‐1,2,4‐triazol‐5‐yl)phenyl}amines. Their structure was ascertained by liquid chromatography–mass spectrometry, 1 H and 13 C NMR, and elemental analysis data. Applying an in vitro growth assay, these triazoles show moderate to significant antifungal activity against the opportunistic pathogen Aspergillus niger , 12 fungi ( Fusarium oxysporum , Fusarium fujikuroi , Colletotrichum higginsianum , Gaeumannomyces graminis , Colletotrichum coccodes , Claviceps purpurea , Alternaria alternata , Mucor indicus , Fusarium graminearum , Verticillium lecanii , Botrytis cinerea , Penicillium digitatum ) and three oomycetes ( Phytophtora infestans GL‐1, P. infestans 4/91; R+ and 4/91; R−) in the concentration range from 1 to 50 µg/ml (0.003–2.1 μM). Frontier molecular orbital energies were determined to predict their genotoxic potential. Molecular docking calculations taking into account six common fungal enzymes point to 14α‐demethylase (CYP51) and N ‐myristoyltransferase as the most probable fungal targets. With respect to effectiveness, structure–activity calculations revealed the strong enhancing impact of adamantyl residues. The shown nonmutagenicity in the Salmonella reverse‐mutagenicity assay and no violations of drug‐likeness parameters suggest the good bioavailability and attractive ecotoxicological profile of the studied triazoles.
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