Ji Dong1,2, Shi-Sheng Huang2, Ya-Nan Hao2, Zi-Wen Wang1, Yu-Xiu Liu2, Yong-Qiang Li2, Qing-Min Wang2. 1. Tianjin Key Laboratory of Structure and Performance for Functional Molecules, MOE Key Laboratory of Inorganic-Organic Hybrid Functional Material Chemistry, College of Chemistry, Tianjin Normal University, Tianjin, China. 2. State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, College of Chemistry, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin, China.
Abstract
BACKGROUND: Food is an important strategic material related to national economy and people's livelihood. Plant diseases seriously affect crop yield and quality. Marine natural products are an important source for novel drugs discovery. In this work, meridianin alkaloids were selected as the parent structure. A series of meridianin alkaloid analogues were rationally designed, synthesized and evaluated for their antiviral activities and fungicidal activities. RESULT: These compounds were found to have good antiviral and fungicidal activities for the first time. The structure-activity relationship (SAR) research revealed that introducing bromine atom at the 5-position of indole ring is beneficial to antiviral activity, but introducing methoxy group is not conducive. Introducing bromine atom at the 6-position of indole ring or nitrogen atom at the 7-position of the indole ring resulted in lower antiviral activity. Most of the meridianin derivatives showed higher anti-TMV activities at 500 μg mL-1 than Ribavirin, especially for compounds 6c, 8a and 10a. All of the compounds also displayed broad spectrum fungicidal activities against 14 kinds of phytopathogenic fungi at 50 μg mL-1 . CONCLUSION: Compound 6c with relatively simple structure and excellent antiviral activity, which is similar to that of Ningnanmycin, emerged as novel anti-TMV lead compound. Compound 5d with broad spectrum and high effect fungicidal activity emerged as a new fungicidal lead compound. Current research lays a solid foundation for the application of meridianin alkaloids in crop protection.
BACKGROUND: Food is an important strategic material related to national economy and people's livelihood. Plant diseases seriously affect crop yield and quality. Marine natural products are an important source for novel drugs discovery. In this work, meridianin alkaloids were selected as the parent structure. A series of meridianin alkaloid analogues were rationally designed, synthesized and evaluated for their antiviral activities and fungicidal activities. RESULT: These compounds were found to have good antiviral and fungicidal activities for the first time. The structure-activity relationship (SAR) research revealed that introducing bromine atom at the 5-position of indole ring is beneficial to antiviral activity, but introducing methoxy group is not conducive. Introducing bromine atom at the 6-position of indole ring or nitrogen atom at the 7-position of the indole ring resulted in lower antiviral activity. Most of the meridianin derivatives showed higher anti-TMV activities at 500 μg mL-1 than Ribavirin, especially for compounds 6c, 8a and 10a. All of the compounds also displayed broad spectrum fungicidal activities against 14 kinds of phytopathogenic fungi at 50 μg mL-1 . CONCLUSION: Compound 6c with relatively simple structure and excellent antiviral activity, which is similar to that of Ningnanmycin, emerged as novel anti-TMV lead compound. Compound 5d with broad spectrum and high effect fungicidal activity emerged as a new fungicidal lead compound. Current research lays a solid foundation for the application of meridianin alkaloids in crop protection.