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Synthesis and Biological Evaluation of Norcantharidin Derivatives Possessing an Aromatic Amine Moiety as Antifungal Agents

Based on the structure of naturally produced cantharidin, different arylamine groups were linked to the norcantharidin scaffold to provide thirty six compounds. Their structures were confirmed by melting point, (1)H-NMR, (13)C-NMR and HRMS-ESI studies. These synthetic compounds were tested as fungis...

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Autores principales: Wang, Yang, Sun, Wenbo, Zha, Shunqing, Wang, Huan, Zhang, Yalin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331962/
https://www.ncbi.nlm.nih.gov/pubmed/26633341
http://dx.doi.org/10.3390/molecules201219782
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author Wang, Yang
Sun, Wenbo
Zha, Shunqing
Wang, Huan
Zhang, Yalin
author_facet Wang, Yang
Sun, Wenbo
Zha, Shunqing
Wang, Huan
Zhang, Yalin
author_sort Wang, Yang
collection PubMed
description Based on the structure of naturally produced cantharidin, different arylamine groups were linked to the norcantharidin scaffold to provide thirty six compounds. Their structures were confirmed by melting point, (1)H-NMR, (13)C-NMR and HRMS-ESI studies. These synthetic compounds were tested as fungistatic agents against eight phytopathogenic fungi using the mycelium growth rate method. Of these thirty six derivatives, seven displayed stronger antifungal activity than did norcantharidin, seven showed higher activity than did cantharidin and three exhibited more significant activity than that of thiabendazole. In particular, 3-(3′-chloro-phenyl)carbamoyl norcantharidate II-8 showed the most significant fungicidal activity against Sclerotinia fructigena and S. sclerotiorum, with IC(50) values of 0.88 and 0.97 μg/mL, respectively. The preliminary structure-activity relationship data of these compounds revealed that: (1) the benzene ring is critical for the improvement of the spectrum of antifungal activity (3-phenylcarbamoyl norcantharidate II-1 vs norcantharidin and cantharidin); (2) among the three sites, including the C-2′, C-3′ and C-4′ positions of the phenyl ring, the presence of a halogen atom at the C-3′position of the benzene ring caused the most significant increase in antifungal activity; (3) compounds with strongly electron-drawing or electron-donating groups substitutions were found to have a poor antifungal activity; and (4) compared with fluorine, bromine and iodine, chlorine substituted at the C-3′ position of the benzene ring most greatly promoted fungistatic activity. Thus, compound II-8 has emerged as new lead structure for the development of new fungicides.
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spelling pubmed-63319622019-01-24 Synthesis and Biological Evaluation of Norcantharidin Derivatives Possessing an Aromatic Amine Moiety as Antifungal Agents Wang, Yang Sun, Wenbo Zha, Shunqing Wang, Huan Zhang, Yalin Molecules Article Based on the structure of naturally produced cantharidin, different arylamine groups were linked to the norcantharidin scaffold to provide thirty six compounds. Their structures were confirmed by melting point, (1)H-NMR, (13)C-NMR and HRMS-ESI studies. These synthetic compounds were tested as fungistatic agents against eight phytopathogenic fungi using the mycelium growth rate method. Of these thirty six derivatives, seven displayed stronger antifungal activity than did norcantharidin, seven showed higher activity than did cantharidin and three exhibited more significant activity than that of thiabendazole. In particular, 3-(3′-chloro-phenyl)carbamoyl norcantharidate II-8 showed the most significant fungicidal activity against Sclerotinia fructigena and S. sclerotiorum, with IC(50) values of 0.88 and 0.97 μg/mL, respectively. The preliminary structure-activity relationship data of these compounds revealed that: (1) the benzene ring is critical for the improvement of the spectrum of antifungal activity (3-phenylcarbamoyl norcantharidate II-1 vs norcantharidin and cantharidin); (2) among the three sites, including the C-2′, C-3′ and C-4′ positions of the phenyl ring, the presence of a halogen atom at the C-3′position of the benzene ring caused the most significant increase in antifungal activity; (3) compounds with strongly electron-drawing or electron-donating groups substitutions were found to have a poor antifungal activity; and (4) compared with fluorine, bromine and iodine, chlorine substituted at the C-3′ position of the benzene ring most greatly promoted fungistatic activity. Thus, compound II-8 has emerged as new lead structure for the development of new fungicides. MDPI 2015-12-02 /pmc/articles/PMC6331962/ /pubmed/26633341 http://dx.doi.org/10.3390/molecules201219782 Text en © 2015 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wang, Yang
Sun, Wenbo
Zha, Shunqing
Wang, Huan
Zhang, Yalin
Synthesis and Biological Evaluation of Norcantharidin Derivatives Possessing an Aromatic Amine Moiety as Antifungal Agents
title Synthesis and Biological Evaluation of Norcantharidin Derivatives Possessing an Aromatic Amine Moiety as Antifungal Agents
title_full Synthesis and Biological Evaluation of Norcantharidin Derivatives Possessing an Aromatic Amine Moiety as Antifungal Agents
title_fullStr Synthesis and Biological Evaluation of Norcantharidin Derivatives Possessing an Aromatic Amine Moiety as Antifungal Agents
title_full_unstemmed Synthesis and Biological Evaluation of Norcantharidin Derivatives Possessing an Aromatic Amine Moiety as Antifungal Agents
title_short Synthesis and Biological Evaluation of Norcantharidin Derivatives Possessing an Aromatic Amine Moiety as Antifungal Agents
title_sort synthesis and biological evaluation of norcantharidin derivatives possessing an aromatic amine moiety as antifungal agents
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331962/
https://www.ncbi.nlm.nih.gov/pubmed/26633341
http://dx.doi.org/10.3390/molecules201219782
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