Design, synthesis and antifungal activity evaluation of isocryptolepine derivatives
| Autor: | Wang Renxuan, Zhong-Min Zhao, Yin-Fang Yan, Peng Jingwen, Xiao-Fei Shang, Jun-Cai Li, Guan-fang Hu, Rui Zhou, Yu Sun, Ying-Qian Liu, Jia-Kai Zhu, Yu-Ling Wang |
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| Rok vydání: | 2019 |
| Předmět: |
Antifungal Agents
Microbial Sensitivity Tests 01 natural sciences Biochemistry Indole Alkaloids chemistry.chemical_compound Structure-Activity Relationship Drug Discovery Quinazoline Structure–activity relationship Mode of action Molecular Biology Mycelium EC50 chemistry.chemical_classification Reactive oxygen species Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry Organic Chemistry Fungi Plants In vitro 0104 chemical sciences Fungicides Industrial Fungicide 010404 medicinal & biomolecular chemistry chemistry Drug Design Quinolines Nuclear chemistry |
| Zdroj: | Bioorganic chemistry. 92 |
| ISSN: | 1090-2120 |
| Popis: | In this paper, the nitrogen atom was inserted into the anthracycline system of the isocryptolepine nucleus to obtain the “Aza”-type structure benzo[4,5]imidazo[1,2-c] quinazoline. A series of “Aza”-type derivatives were designed, synthesized and evaluated for their antifungal activity against six plant fungi in vitro. Among all derivatives, compounds A-0, B-1 and B-2 showed significant antifungal activity against B. cinerea with the EC50 values of 2.72 μg/mL, 5.90 μg/mL and 4.00 μg/mL, respectively. Compound A-2 had the highest activity against M. oryzae with the EC50 values of 8.81 μg/mL, and compound A-1 demonstrated the most control efficacy against R. solani (EC50, 6.27 μg/mL). Moreover, compound A-0 was selected to investigate the in vivo tests against B. cinerea and the results indicated that the preventative efficacy of it up to 72.80% at 100 μg/mL. Preliminary mechanism studies revealed that after treatment with A-0 at 5 µg/mL, the B. cinerea mycelia appeared curved, collapsed and the cell membrane integrity may be damaged. The reactive oxygen species production, mitochondrial membrane potential and nuclear morphometry of mycelia have been changed, and the membrane function and cell proliferation of mycelia were destroyed. Compounds A-0, A-1, B-1 and B-2 presented weaker toxicities against two cells lines than isocryptolepine. This study lays the foundation for the future development of isocryptolepine derivatives as environmentally friendly and safe agricultural fungicides. |
| Databáze: | OpenAIRE |
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