Article pubs.acs.org/JAFC
Discovery of Topsentin Alkaloids and Their Derivatives as Novel Antiviral and Anti-phytopathogenic Fungus Agents Xiaofei Ji,†,§ Ziwen Wang,*,† Ji Dong,§ Yuxiu Liu,§ Aidang Lu,§ and Qingmin Wang*,§ †
Tianjin Key Laboratory of Structure and Performance for Functional Molecules, Key Laboratory of Inorganic−Organic Hybrid Functional Materials Chemistry (Tianjin Normal University), Ministry of Education, College of Chemistry, Tianjin Normal University, Tianjin 300387, China § State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin 300071, China S Supporting Information *
ABSTRACT: Topsentin alkaloids and their derivatives were designed, synthesized, and characterized on the basis of NMR and mass spectroscopy. The antiviral activities against tobacco mosaic virus (TMV) and anti-phytopathogenic fungus activities of these alkaloids were evaluated for the first time. Alkaloids 1c, 1e, 2b, and 2d displayed significantly higher antiviral activities against TMV than Ribavirin, emerging as new lead compounds for anti-TMV research. Further fungicidal activity tests against 14 kinds of phytopathogenic fungi revealed that these alkaloids displayed broad-spectrum fungicidal activities. Topsentin derivative 2d with 4−5 mg/kg EC50 values against Sclerotinia sclerotiorum (Lib.), Rhizoctonia solani (Kuhn), and Botrytis cinerea (Pers.) emerged as a new lead compound for fungicidal research. Current studies provide support for the application of topsentin alkaloids as novel agrochemicals. KEYWORDS: topsentin alkaloids, natural product, anti-TMV activity, antifungal activity, agrochemical
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INTRODUCTION Plant diseases, caused by viral pathogens, fungi, bacteria, and oomycetes, always affect people’s daily life and health.1−3 Tobacco mosaic virus (TMV) is the earliest discovered and most well-studied plant virus.3 It is known to infect at least 125 individual plant species, such as tobacco, peppers, tomatos, cucumbers, ornamental flowers, and so on.3 Furthermore, TMV can be used as the template virus for the discovery of antiviral agents for other viruses. For example, phenanthroindolizidine alkaloids with anti-TMV activities were also found to have good human immunodeficiency virus inhibitory effect.4 Banana panama diseases, caused by the fungus Fusarium oxysporum, led to enormous costs to the world in the 1950s.1 The late blight caused by the oomycete Phytophthora infestans led to the Irish potato famine in the 1840s.1 The rust diseases of wheat, caused by rust fungi Puccinia graminis and Puccinia Striiformis, are the most common and widespread diseases of wheat worldwide.1 Plant pathogens can propagate rapidly via wind, insects, water, and humans over great distances. Therefore, plant diseases, caused by viral, fungal, and bacterial pathogens, are known as “plant cancer”. The protection of plants from these diseases is very difficult.3 Ribavirin (Figure 1), a successfully registered antiviral agent, is widely used for preventing TMV diseases.5 Nevertheless, the antiviral effect of Ribavirin is
