Natural Products-Based Fungicides: Synthesis and Antifungal Activity against Plant Pathogens of 2H-Chromene Derivatives
Wenjing Liu
College of Pharmacy, Guizhou Provincial Engineering Technology Research Center for Chemical Drug R&D, Guizhou Provincial Key Laboratory of Pathogenesis and Drug Research on Common Chronic Diseases, Guizhou Medical University, Guiyang, 550004 P. R. China
Search for more papers by this authorYong Li
College of Pharmacy, Guizhou Provincial Engineering Technology Research Center for Chemical Drug R&D, Guizhou Provincial Key Laboratory of Pathogenesis and Drug Research on Common Chronic Diseases, Guizhou Medical University, Guiyang, 550004 P. R. China
Search for more papers by this authorJudi Fan
College of Pharmacy, Guizhou Provincial Engineering Technology Research Center for Chemical Drug R&D, Guizhou Provincial Key Laboratory of Pathogenesis and Drug Research on Common Chronic Diseases, Guizhou Medical University, Guiyang, 550004 P. R. China
Search for more papers by this authorLei Tang
College of Pharmacy, Guizhou Provincial Engineering Technology Research Center for Chemical Drug R&D, Guizhou Provincial Key Laboratory of Pathogenesis and Drug Research on Common Chronic Diseases, Guizhou Medical University, Guiyang, 550004 P. R. China
Search for more papers by this authorBing Guo
College of Pharmacy, Guizhou Provincial Engineering Technology Research Center for Chemical Drug R&D, Guizhou Provincial Key Laboratory of Pathogenesis and Drug Research on Common Chronic Diseases, Guizhou Medical University, Guiyang, 550004 P. R. China
Search for more papers by this authorWei Xue
Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Guiyang, 550025 P. R. China
Search for more papers by this authorCorresponding Author
Lingling Fan
College of Pharmacy, Guizhou Provincial Engineering Technology Research Center for Chemical Drug R&D, Guizhou Provincial Key Laboratory of Pathogenesis and Drug Research on Common Chronic Diseases, Guizhou Medical University, Guiyang, 550004 P. R. China
Search for more papers by this authorWenjing Liu
College of Pharmacy, Guizhou Provincial Engineering Technology Research Center for Chemical Drug R&D, Guizhou Provincial Key Laboratory of Pathogenesis and Drug Research on Common Chronic Diseases, Guizhou Medical University, Guiyang, 550004 P. R. China
Search for more papers by this authorYong Li
College of Pharmacy, Guizhou Provincial Engineering Technology Research Center for Chemical Drug R&D, Guizhou Provincial Key Laboratory of Pathogenesis and Drug Research on Common Chronic Diseases, Guizhou Medical University, Guiyang, 550004 P. R. China
Search for more papers by this authorJudi Fan
College of Pharmacy, Guizhou Provincial Engineering Technology Research Center for Chemical Drug R&D, Guizhou Provincial Key Laboratory of Pathogenesis and Drug Research on Common Chronic Diseases, Guizhou Medical University, Guiyang, 550004 P. R. China
Search for more papers by this authorLei Tang
College of Pharmacy, Guizhou Provincial Engineering Technology Research Center for Chemical Drug R&D, Guizhou Provincial Key Laboratory of Pathogenesis and Drug Research on Common Chronic Diseases, Guizhou Medical University, Guiyang, 550004 P. R. China
Search for more papers by this authorBing Guo
College of Pharmacy, Guizhou Provincial Engineering Technology Research Center for Chemical Drug R&D, Guizhou Provincial Key Laboratory of Pathogenesis and Drug Research on Common Chronic Diseases, Guizhou Medical University, Guiyang, 550004 P. R. China
Search for more papers by this authorWei Xue
Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Guiyang, 550025 P. R. China
Search for more papers by this authorCorresponding Author
Lingling Fan
College of Pharmacy, Guizhou Provincial Engineering Technology Research Center for Chemical Drug R&D, Guizhou Provincial Key Laboratory of Pathogenesis and Drug Research on Common Chronic Diseases, Guizhou Medical University, Guiyang, 550004 P. R. China
Search for more papers by this authorAbstract
Aiming to search for novel potential antifungal agents, forty 2H-chromene analogs were designed, synthesized and their antifungal activity against some typical plant pathogenic fungi were firstly evaluated. The in vitro antifungal bioassays showed that some of the target compounds exhibited comparable or better inhibition activities than the commercial agricultural fungicide hymexazol. Especially compound 1m displayed more promising fungicidal effect against Alternaria alternate (EC50=9.9 μg/mL) and Botrytis cinerea (EC50=9.4 μg/mL), which was significantly superior to hymexazol. Moreover, in vivo protective effects results also indicated that compound 1m had an excellent potential for further development as a new botanical pesticide.
Graphical Abstract
Conflict of interest
The authors declare that they have no conflict of interest.
Open Research
Data Availability Statement
The data that support the findings of this study are available in the supplementary material of this article.
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References
- 1V. S. Brauer, C. P. Rezende, A. M. Pessoni, R. G. D. Paula, K. S. Rangappa, S. C. Nayaka, V. K. Gupta, F. Almeida, ‘Antifungal agents in agriculture: friends and foes of public healthy’, Biomol. Eng. 2019, 9, 521.
- 2S. Brase, A. Encinas, J. Keck, C. F. Nising, ‘Chemistry and biology of mycotoxins and related fungal metabolites’, Chem. Rev. 2009, 109, 3903–3990.
- 3L. Ons, D. Bylemans, K. Thevissen, B. P. A. Cammue, ‘Combining biocontrol agents with chemical fungicides for integrated plant fungal disease control’, Microorganisms 2020, 8, 1930.
- 4J. Jampilek, ‘Novel avenues for identification of new antifungal drugs and current challenges’, Expert Opin. Drug Discovery 2022.
- 5R. Pratap, V. J. Ram, ‘Natural and synthetic chromenes, fused chromenes, and versatility of dihydrobenzo[h]chromenes in organic synthesis’, Chem. Rev. 2014, 114, 10476–10526.
- 6W. S. Wu, H. Y. Ye, L. Wan, X. L. Han, G. C. Wang, J. Hu, M. H. Tang, X. M. Duan, Y. Fan, S. C. He, L. Huang, H. Y. Pei, X. W. Wang, X. X. Li, C. F. Xie, R. G. Zhang, Z. Yuan, Y. Q. Mao, Y. Q. Wei, L. J. Chen, ‘Millepachine, a novel chalcone, induces G2/M arrest by inhibiting CDK1 activity and causing apoptosis via ROS-mitochondrial apoptotic pathway in human hepatocarcinoma cells in vitro and in vivo’, Carcinogenesis 2013, 34, 1636–1643.
- 7A. Satoh, H. Utamura, M. Ishizuka, N. Endo, M. Tsuji, H. Nishimura, ‘Antimicrobial benzopyrans from the receptacle of sunflower’, Biosci. Biotechnol. Biochem. 1996, 60, 664–665.
- 8Y. Li, B. L. Luo, Z. F. Luo, T. G. Ma, L. L. Fan, W. J. Liu, J. D. Fan, B. Guo, W. Xue, L. Tang, ‘Design and synthesis of novel 2,2-dimethylchromene derivatives as potential antifungal agents’, Mol. Diversity 2022.
- 9H. Xu, L. L. Fan, ‘Antifungal agents. Part 4: Synthesis and antifungal activities of novel indole[1,2-c]-1,2,4-benzotriazine derivatives against phytopathogenic fungi in vitro’, Eur. J. Med. Chem. 2011, 46, 364–369.
- 10H. Xu, L. L. Fan, ‘Synthesis and antifungal activities of novel 5,6-dihydroindolo-[1,2-a]quinoxaline derivatives’, Eur. J. Med. Chem. 2011, 46, 1919–1925.
- 11Y. Li, Z. F. Luo, B. L. Luo, Q. Lan, J. D. Fan, W. Xue, J. Miao, Y. Li, L. Tang, L. L. Fan, ‘Design, synthesis and antifungal activities of 6-substituted 3-butylphthalide derivatives against phytopathogenic fungi’, Chem. Biodiversity 2020, 17, e2000435.
- 12L. L. Fan, Z. F. Luo, Y. Li, X. Y. Liu, J. D. Fan, W. Xue, L. Tang, Y. Li, ‘Synthesis and antifungal activity of imidazo[1,2-b]pyridazine derivatives against phytopathogenic fungi’, Bioorg. Med. Chem. Lett. 2020, 30, 127139.
- 13L. L. Fan, Z. F. Luo, C. F. Yang, L. Tang, Y. Li, ‘Design and synthesis of small molecular 2-aminobenzoxazoles as potential antifungal agents against phytopathogenic fungi’, Mol. Diversity 2022, 26, 981–992.
- 14Y. Cohen, A, Rubin, D. Gotlieb, ‘Activity of carboxylic acid amide (CAA) fungicides against Bremia lactucae’, Eur. J. Plant Pathol. 2008, 122, 169–183.
- 15C. J. Liu, H. Y. Zhang, L. X. Sun, L. J. Guan, ‘Effects of isobavachalcone on the resistance to TMV and activity of defense enzymes of tobacco’, Agrochemia 2022.
- 16D. Cao, X. L. Han, G. C. Wang, Z. Yang, F. Peng, L. Ma, R. H. Zhang, H. Y. Ye, M. H. Tang, W. S. Wu, K. Lei, J. L. Wen, J. Y. Chen, J. X. Qiu, X. L. Liang, Y. Ran, Y. Sang, M. L. Xiang, A. H. Peng, L. J. Chen, ‘Synthesis and biological evaluation of novel pyranochalcone derivatives as a new class of microtubule stabilizing agents’, Eur. J. Med. Chem. 2013, 62, 579–589.
- 17T. Li, J. J. Song, L. H. Wang, T. Lei, S. Z. Jiang, F. S. Wang, ‘A simple and efficient total synthesis of anticancer indole alkaloids TMC-205 and its analogs’, Tetrahedron Lett. 2021, 74, 153137.
- 18D. C. Erwin, J. J. Sims, D. E. Borum, J. R. Childers, ‘Detection of the systemic fungicide, thiabendazole, in cotton plants and soil by chemical analysis and bioassay’, Phytopathology 1971, 61, 964–967.
- 19X. L. Fang, Z. Z. Li, Y. H. Wang, X. Zhang, ‘In vitro and in vivo antimicrobial activity of Xenorhabdus bovienii YL002 against Phytophthora capsici and Botrytis cinerea’, J. Appl. Microbiol. 2011, 111, 145–154.
- 20H. H. Wen, Y. Q. Zhang, X. H. Wang, X. P. Zeng, Z. X. Hu, Y. Liu, Y. X. Xie, G. Y. Liang, J. G. Zhu, H. Luo, B. X. Xu, ‘Novel 3′,5′-diprenylated chalcones inhibited the proliferation of cancer cells in vitro by inducing cell apoptosis and arresting cell cycle phase’, Eur. J. Med. Chem. 2017, 133, 227–239.
- 21G. C. Wang, W. S. Wu, F. Peng, D. Cao, Z. Yang, L. Ma, N. Qiu, H. Y. Ye, X. L. Han, J. Y. Chen, J. X. Qiu, Y. Sang, X. L. Liang, Y. Ran, A. H. Peng, Y. Q. Wei, L. J. Chen, ‘Design, synthesis, and structure–activity relationship studies of novel millepachine derivatives as potent antiproliferative agents’, Eur. J. Med. Chem. 2012, 54, 793–803.
