New 2-aryl-7,8-dimethoxy-3,4-dihydroisoquinolin-2-ium salts as potential antifungal agents: synthesis, bioactivity and structure-activity relationships
Abstract The title compounds can be considered as simple analogues of quaternary benzo[c]phenanthridine alkaloids (QBAs). In order to develop potent QBA-like antifungal agents, as our continuing study, a series of new title compounds were synthesized and evaluated for bioactivity against five plant...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2017-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-07303-8 |
| _version_ | 1818429440982515712 |
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| author | Lifei Zhu Bohang Zhou Bingyu Zhang Mingxuan Xu Huiling Geng Le Zhou |
| author_facet | Lifei Zhu Bohang Zhou Bingyu Zhang Mingxuan Xu Huiling Geng Le Zhou |
| author_sort | Lifei Zhu |
| collection | DOAJ |
| description | Abstract The title compounds can be considered as simple analogues of quaternary benzo[c]phenanthridine alkaloids (QBAs). In order to develop potent QBA-like antifungal agents, as our continuing study, a series of new title compounds were synthesized and evaluated for bioactivity against five plant pathogenic fungi by the mycelium growth rate method in this study. The SAR were also derived. The majority of the compounds showed good to excellent inhibition activity with average EC50 values of 7.87–20.0 μM for the fungi, superior to sanguinarine and cherythrine (two QBAs) and the commercial fungicide azoxystrobin. Part of the compounds were more active than commercial fungicides thiabendazole or carbendazim against F. solani, F. graminearum and C. gloeosporioides. Six compounds with average EC50 of 3.5–5.1 μg/mL possessed very great potential for development of new antifungal agents. SAR found that substitution patterns of the two aryl-rings significantly affect the activity. There exists a complex interaction effect between substituents of the two aryl-rings on the activity. Generally, the presence of electron-withdrawing groups on the C-ring can significantly increase the activity. These findings will be of great importance for the design of more potent antifungal isoquinoline agents. |
| first_indexed | 2024-12-14T15:17:34Z |
| format | Article |
| id | doaj.art-4887c97e45974bf0b94608093f6d37c6 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-14T15:17:34Z |
| publishDate | 2017-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-4887c97e45974bf0b94608093f6d37c62022-12-21T22:56:15ZengNature PortfolioScientific Reports2045-23222017-08-017111410.1038/s41598-017-07303-8New 2-aryl-7,8-dimethoxy-3,4-dihydroisoquinolin-2-ium salts as potential antifungal agents: synthesis, bioactivity and structure-activity relationshipsLifei Zhu0Bohang Zhou1Bingyu Zhang2Mingxuan Xu3Huiling Geng4Le Zhou5College of Chemistry & Pharmacy, Northwest A&F UniversityCollege of Chemistry & Pharmacy, Northwest A&F UniversityCollege of Chemistry & Pharmacy, Northwest A&F UniversityCollege of Chemistry & Pharmacy, Northwest A&F UniversityCollege of Chemistry & Pharmacy, Northwest A&F UniversityCollege of Chemistry & Pharmacy, Northwest A&F UniversityAbstract The title compounds can be considered as simple analogues of quaternary benzo[c]phenanthridine alkaloids (QBAs). In order to develop potent QBA-like antifungal agents, as our continuing study, a series of new title compounds were synthesized and evaluated for bioactivity against five plant pathogenic fungi by the mycelium growth rate method in this study. The SAR were also derived. The majority of the compounds showed good to excellent inhibition activity with average EC50 values of 7.87–20.0 μM for the fungi, superior to sanguinarine and cherythrine (two QBAs) and the commercial fungicide azoxystrobin. Part of the compounds were more active than commercial fungicides thiabendazole or carbendazim against F. solani, F. graminearum and C. gloeosporioides. Six compounds with average EC50 of 3.5–5.1 μg/mL possessed very great potential for development of new antifungal agents. SAR found that substitution patterns of the two aryl-rings significantly affect the activity. There exists a complex interaction effect between substituents of the two aryl-rings on the activity. Generally, the presence of electron-withdrawing groups on the C-ring can significantly increase the activity. These findings will be of great importance for the design of more potent antifungal isoquinoline agents.https://doi.org/10.1038/s41598-017-07303-8 |
| spellingShingle | Lifei Zhu Bohang Zhou Bingyu Zhang Mingxuan Xu Huiling Geng Le Zhou New 2-aryl-7,8-dimethoxy-3,4-dihydroisoquinolin-2-ium salts as potential antifungal agents: synthesis, bioactivity and structure-activity relationships Scientific Reports |
| title | New 2-aryl-7,8-dimethoxy-3,4-dihydroisoquinolin-2-ium salts as potential antifungal agents: synthesis, bioactivity and structure-activity relationships |
| title_full | New 2-aryl-7,8-dimethoxy-3,4-dihydroisoquinolin-2-ium salts as potential antifungal agents: synthesis, bioactivity and structure-activity relationships |
| title_fullStr | New 2-aryl-7,8-dimethoxy-3,4-dihydroisoquinolin-2-ium salts as potential antifungal agents: synthesis, bioactivity and structure-activity relationships |
| title_full_unstemmed | New 2-aryl-7,8-dimethoxy-3,4-dihydroisoquinolin-2-ium salts as potential antifungal agents: synthesis, bioactivity and structure-activity relationships |
| title_short | New 2-aryl-7,8-dimethoxy-3,4-dihydroisoquinolin-2-ium salts as potential antifungal agents: synthesis, bioactivity and structure-activity relationships |
| title_sort | new 2 aryl 7 8 dimethoxy 3 4 dihydroisoquinolin 2 ium salts as potential antifungal agents synthesis bioactivity and structure activity relationships |
| url | https://doi.org/10.1038/s41598-017-07303-8 |
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