Synthesis and antiphytoviral activity of α-aminophosphonates containing 3, 5-diphenyl-2-isoxazoline as potential papaya ringspot virus inhibitors
- 113 Downloads
α-Aminophosphonates compounds containing 3,5-diphenyl-2-isoxazoline were synthesized and evaluated for their bioactivity. Seventeen of them showed good bioactivity (protection effect > 50%) in vivo against papaya ringspot virus, while two of them (V29 and V45) exhibited excellent antiviral activity (both 77.8%). In the latter case, the antiviral activity was close to that of antiphytovirucides ningnanmycin and dufulin (both 83.3%) at 500 mg/L. The preliminary structure–activity relationships indicated that the bioactivity was strongly influenced by the substituents.
Keywordsα-Aminophosphonates 3, 5-Diphenyl-2-isoxazoline Synthesis Anti-PRSV activity Structure–activity relationships
This work was financially supported by the National Natural Science Foundation of China (Grant No. 31601675) and the Specialized Research Fund for the Doctoral Program of Education of China (Grant No. 20134404130003). We thank Dr. Xueqin Rao (Department of Plant Pathology, South China Agricultural University) and Dr. Duo Lai (Institute of Fruit Tree Research, Guangdong Academy of Agricultural Sciences, China) for their kind help in screening the compounds for biological activity.
- 7.Tripathi S, Suzuki J, Gonsalves D (2007) Development of genetically engineered resistant papaya for papaya ringspot virus in a timely manner: a comprehensive and successful approach. Plant-pathogen interactions: methods and protocols 354:197–240. https://doi.org/10.1385/1-59259-966-4:197 CrossRefGoogle Scholar
- 11.Yu XL, Wei P, Wang ZW, Liu YX, Wang LZ, Wang QM (2016) Design, synthesis, antiviral activity and mode of action of phenanthrene-containing N-heterocyclic compounds inspired by the phenanthroindolizidine alkaloid antofine. Pest Manag Sci 72:371–378. https://doi.org/10.1002/ps.4008 CrossRefPubMedPubMedCentralGoogle Scholar
- 12.Chen RY, Dai Q, Zhang D, Yang XF (1995) Synthesis of O, O-diethyl-α-(p-toluenesulphonamido) phosphonates by Mannich-type reaction. Sci China, Ser B 38:1153–1157Google Scholar
- 16.Zeng ZG, Yan Y, Wang BF, Liu N, Xu HH (2017) Discovery and identification of O, O-diethyl O-(4-(5-phenyl-4,5-dihydroisoxazol-3-yl) phenyl) phosphorothioate (XP-1408) as a novel mode of action of organophosphorus insecticides. Sci Rep 7:3617. https://doi.org/10.1038/s41598-017-03663-3 CrossRefPubMedPubMedCentralGoogle Scholar
- 19.Olson RE, Sielecki TM, Wityak J, Pinto DJ, Batt DG, Frietze WE, Liu J, Tobin AE, Orwat MJ, Di Meo SV, Houghton GC, Lalka GK, Mousa SA, Racanelli AL, Hausner EA, Kapil RP, Rabel SR, Thoolen MJ, Reilly TM, Anderson PS, Wexler RR (1999) Orally active isoxazoline glycoprotein IIb/IIIa antagonists with extended duration of action. J Med Chem 42:1178–1192. https://doi.org/10.1021/jm980348t CrossRefPubMedPubMedCentralGoogle Scholar
- 24.Van Der Puy M (2000). Process for the preparation of trifluoropropanal. US Pat 6111139Google Scholar
- 27.Zeng ZG, Luo YP (2011) Process improvement on the synthesis of ethyl 2-aminoquinoline-3-carboxylate. Fine Chem Intermediat 41:24–26 (in Chinese) Google Scholar
- 30.Chávez-Calvillo G, Contreras-Paredes CA, Mora-Macias J, Noa-Carrazana JC, Serrano-Rubio AA, Dinkova TD, Carrillo-Tripp M, Silva-Rosales L (2016) Antagonism or synergism between papaya ringspot virus and papaya mosaic virus in Carica papaya is determined by their order of infection. Virology 489:179–191. https://doi.org/10.1016/j.virol.2015.11.026 CrossRefPubMedPubMedCentralGoogle Scholar
- 31.Nakamura K, Akiyama H, Takahashi Y, Takahashi T, Noguchi A, Ohmori K, Kasahara M, Kitta K, Nakazawa H, Kondo K, Teshima R (2013) Application of a qualitative and quantitative real-time polymerase chain reaction method for detecting genetically modified papaya line 55-1 in papaya products. Food Chem 136:895–901. https://doi.org/10.1016/j.foodchem.2012.08.088 CrossRefPubMedPubMedCentralGoogle Scholar