Article pubs.acs.org/JAFC
Cite This: J. Agric. Food Chem. XXXX, XXX, XXX−XXX
Marine Natural Products for Drug Discovery: First Discovery of Kealiinines A−C and Their Derivatives as Novel Antiviral and Antiphytopathogenic Fungus Agents Gang Li,†,‡ Jincheng Guo,‡ Ziwen Wang,*,† Yuxiu Liu,*,‡ Haibin Song,‡ and Qingmin Wang*,‡
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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, College of Chemistry, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin 300071, China S Supporting Information *
ABSTRACT: Leucetta alkaloid kealiinines A−C and kealiinine B derivatives were designed, synthesized, and characterized on the basis of NMR and HR-MS. The anti-TMV and antiphytopathogenic fungus activities of these alkaloids were evaluated for the first time. Kealiinine B exhibited a higher anti-TMV activity than kealiinines A and C. Kealiinine B derivatives 2m (inhibitory rates: 68, 66, and 71% at 500 μg/mL for inactivation, curative, and protection activity in vivo, respectively) and 2y (inhibitory rates: 69, 64, and 63% at 500 μg/mL for inactivation, curative, and protection activity in vivo, respectively) showed significantly higher antiviral activity than ningnanmycin (inhibitory rates: 56, 56, and 58% at 500 μg/mL for inactivation, curative, and protection activity in vivo, respectively), thus emerging as new lead compounds for novel antiviral agent development. Structure−activity relationship research provided the basis for structural simplification of these alkaloids. Further fungicidal activity tests revealed that these alkaloids displayed broad-spectrum fungicidal activities. Compounds 2i and 2p displayed good fungicidal activities in vitro against Sclerotinia sclerotiorum and Rhizoctonia cerealis with inhibition rates of 71%/ 50 mg/kg and 70%/50 mg/kg, respectively. KEYWORDS: marine natural products, Leucetta alkaloids, kealiinines, anti-TMV activity, fungicidal activity
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INTRODUCTION The global issues of food, population, resources, and environment are critical problems facing humans in the 21st century. According to the recent population survey, the global population has been predicted to exceed roughly 9 billion by 2050, with an estimated crop demand rise of 100−110%.1,2 However, the goal of doubling global crop production cannot be achieved by the middle of this century.3 Although several effective measures, like developing intensive agriculture,4 utilizing biotechnology,5,6 and applying chlorophyll fluorescence,7 have been put forward to solve the above problem, the role of pesticides in reducing crop loss caused by plant diseases and pests cannot be overlooked.8 Historically, losses of crop yield from plant virus diseases have had severe effects on the human race via famines and epidemics.9 Tobacco Mosaic Virus (TMV), one well-studied plant virus, can infect more than 125 plant species like tobacco, tomato, pepper, etc.10 The successfully registered plant viral inhibitors, ribavirin (
