Login Register Cart 0
Generic placeholder image

Current Organic Synthesis

Editor-in-Chief

ISSN (Print): 1570-1794
ISSN (Online): 1875-6271

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Discovery of Resveratrol and its Derivatives as Novel Antiviral and Anti- Phytopathogenic-Fungus Agents

Author(s): Zongwei Xia, Xiuling Yu*, Feng Feng*, Pengfei Song, Wenqiang Yang, Jiacai Wang and Qingmin Wang*

Volume 20, Issue 3, 2023

Published on: 08 November, 2022

Page: [351 - 359] Pages: 9

DOI: 10.2174/1570179420666221005124445

Price: $65

Abstract

Background: Plant diseases caused by viruses and pathogens have posed a serious threat to global agricultural production and are difficult to control. Natural products have always been a valuable source for lead discovery in medicinal and agricultural chemistry. The natural product resveratrol was found to have good antiviral activity against the tobacco mosaic virus (TMV) and fungicidal activities against 14 kinds of phytopathogenic fungi.

Objective: The aim of this work was to design, synthesize a series of derivatives of resveratrol, and evaluate their antiviral and fungicidal activities systematically.

Methods: Novel resveratrol sulfonate derivatives were prepared by a convenient synthesis method from resveratrol, alkyl sulfonyl chloride, aryl sulfonyl chloride, and heterocyclic sulfonyl chloride. Their structures were also identified by nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry (HRMS).

Results: Most of the targets were obtained at a high yield. Compounds I-2, I-5, I-10, II-2, and II-4, with excellent antiviral activities, showed higher anti-TMV activities than those of lead compounds and commercial ribavirin (inhibitory rates of 38, 37, and 38% at 500 μg/mL for inactivation, curative, and protection activities in vivo, respectively). In particular, compounds I-5, I-10, II-2, and II-4 displayed similar inhibitory effects as ningnanmycin (inhibitory rates of 54, 56, and 58% at 500 μg/mL for inactivation, curative, and protection activities in vivo, respectively), the best antiviral agent at present, thereby emerging as new antiviral pilot compounds. Further fungicidal activity tests showed that resveratrol derivatives also displayed broad-spectrum fungicidal activities.

Conclusion: The anti-TMV activities of these compounds were discovered for the first time. Some of these simply structured compounds showed higher TMV inhibitory effects than ribavirin. The current study provided valuable insights into the antiviral and fungicidal activities of resveratrol derivatives, but more modification of the structure should be conducted.

Keywords: resveratrol, lead compound, structural modification, anti-TMV activity, fungicidal activity, structure–activity relationships.

« Previous
Graphical Abstract

[1]
Savary, S.; Willocquet, L.; Pethybridge, S.J.; Esker, P.; McRoberts, N.; Nelson, A. The global burden of pathogens and pests on major food crops. Nat. Ecol. Evol., 2019, 3(3), 430-439.
[http://dx.doi.org/10.1038/s41559-018-0793-y] [PMID: 30718852]
[2]
Butler, P.J.G. The current picture of the structure and assembly of tobacco mosaic virus. J. Gen. Virol., 1984, 65(2), 253-279.
[http://dx.doi.org/10.1099/0022-1317-65-2-253] [PMID: 6363621]
[3]
Lu, A.; Wang, T.; Hui, H.; Wei, X.; Cui, W.; Zhou, C.; Li, H.; Wang, Z.; Guo, J.; Ma, D.; Wang, Q. Natural products for drug discovery: Discovery of gramines as novel agents against a plant virus. J. Agric. Food Chem., 2019, 67(8), 2148-2156.
[http://dx.doi.org/10.1021/acs.jafc.8b06859] [PMID: 30730738]
[4]
Song, B.A.; Yang, S.; Jin, L.H.; Bhadury, P.S. Environment Friendly Anti-plant Viral Agents; Chemical Industry Press and Springer Press: Beijing, China, 2009.
[5]
Liu, L.R. The Control of Disease and Pests of Tobacco; Science Press: Beijing, China, 1998, p. 31.
[6]
Rodrigues, T.; Reker, D.; Schneider, P.; Schneider, G. Counting on natural products for drug design. Nat. Chem., 2016, 8(6), 531-541.
[http://dx.doi.org/10.1038/nchem.2479] [PMID: 27219696]
[7]
Wang, S.; Dong, G.; Sheng, C. Structural simplification of natural products. Chem. Rev., 2019, 119(6), 4180-4220.
[http://dx.doi.org/10.1021/acs.chemrev.8b00504] [PMID: 30730700]
[8]
Wu, W.; Tang, Y.; Yang, J.; Idehen, E.; Sang, S. Avenanthramide aglycones and glucosides in oat bran: Chemical profile, levels in commercial oat products, and cytotoxicity to human colon cancer cells. J. Agric. Food Chem., 2018, 66(30), 8005-8014.
[http://dx.doi.org/10.1021/acs.jafc.8b02767] [PMID: 29985603]
[9]
Duggar, B.M.; Armstrong, J.K. The effect of treating the virus of tobacco mosaic with the juices of various plants. Ann. Mo. Bot. Gard., 1925, 12(4), 359-366.
[http://dx.doi.org/10.2307/2394061]
[10]
Ouyang, M.A.; Wein, Y.S.; Zhang, Z.K.; Kuo, Y.H. Inhibitory activity against Tobacco Mosaic Virus (TMV) replication of pinoresinol and syringaresinol lignans and their glycosides from the root of Rhus javanica var. roxburghiana. J. Agric. Food Chem., 2007, 55(16), 6460-6465.
[http://dx.doi.org/10.1021/jf0709808] [PMID: 17616139]
[11]
Chen, J.; Yan, X.H.; Dong, J.H.; Sang, P.; Fang, X.; Di, Y.T.; Zhang, Z.K.; Hao, X.J. Tobacco Mosaic Virus (TMV) inhibitors from Picrasma quassioides Benn. J. Agric. Food Chem., 2009, 57(15), 6590-6595.
[http://dx.doi.org/10.1021/jf901632j] [PMID: 19586051]
[12]
Ji, X.; Wang, Z.; Dong, J.; Liu, Y.; Lu, A.; Wang, Q. Discovery of topsentin alkaloids and their derivatives as novel antiviral and anti-phytopathogenic fungus agents. J. Agric. Food Chem., 2016, 64(48), 9143-9151.
[http://dx.doi.org/10.1021/acs.jafc.6b04020] [PMID: 27933985]
[13]
Liu, B.; Li, R.; Li, Y.; Li, S.; Yu, J.; Zhao, B.; Liao, A.; Wang, Y.; Wang, Z.; Lu, A.; Liu, Y.; Wang, Q. Discovery of pimprinine alkaloids as novel agents against aplant virus. J. Agric. Food Chem., 2019, 67(7), 1795-1806.
[http://dx.doi.org/10.1021/acs.jafc.8b06175] [PMID: 30681853]
[14]
Zhao, L.; Zhang, J.; Liu, T.; Mou, H.; Wei, C.; Hu, D.; Song, B. Design, synthesis, and antiviral activities of coumarin derivatives containing dithioacetal structures. J. Agric. Food Chem., 2020, 68(4), 975-981.
[http://dx.doi.org/10.1021/acs.jafc.9b06861] [PMID: 31891504]
[15]
Han, Y.; Luo, Y.; Qin, S.; Xi, L.; Wan, B.; Du, L. Induction of systemic resistance against tobacco mosaic virus by Ningnanmycin in tobacco. Pestic. Biochem. Physiol., 2014, 111, 14-18.
[http://dx.doi.org/10.1016/j.pestbp.2014.04.008] [PMID: 24861928]
[16]
Martinez, M.J.A.; Olmo, L.M.B.D.; Benito, P.B. Antiviral activities of polysaccharides from natural sources. Studies in Nat. Prod. Chem., 2005, 30, 393-418.
[http://dx.doi.org/10.1016/S1572-5995(05)80038-9]
[17]
Takaoka, M.J. of the phenolic substances of white hellebore (Veratrum grandiflorum Loes. fil.). J. Fac. Sci. Hokkaido Imperial Uni., 1940, 3, 101816417.
[18]
Liu, W.B.; Hu, L.; Hu, Q.; Chen, N.N.; Yang, Q.S.; Wang, F.F. New resveratrol oligomer derivatives from the roots of Rheum lhasaense. Molecules, 2013, 18(6), 7093-7102.
[http://dx.doi.org/10.3390/molecules18067093] [PMID: 23778119]
[19]
Fulda, S. Resveratrol and derivatives for the prevention and treatment of cancer. Drug Discov. Today, 2010, 15(17-18), 757-765.
[http://dx.doi.org/10.1016/j.drudis.2010.07.005] [PMID: 20692359]
[20]
Uenobe, F.; Nakamura, S.; Miyazawa, M. Antimutagenic effect of resveratrol against Trp-P-1. Mutat. Res., 1997, 373(2), 197-200.
[http://dx.doi.org/10.1016/S0027-5107(96)00191-1] [PMID: 9042400]
[21]
Creasy, L.L.; Coffee, M. Phytoalexin production potential of grape berries. J. Am. Soc. Hortic. Sci., 1988, 113(2), 230-234.
[http://dx.doi.org/10.21273/JASHS.113.2.230]
[22]
Suh, D.D.; Krauss, J.S.; Bures, K. Influence of hemoglobin S adducts on hemoglobin A2 quantification by HPLC. Clin. Chem., 1996, 42(7), 1113-1114.
[http://dx.doi.org/10.1093/clinchem/42.7.1113] [PMID: 8674201]
[23]
Jeandet, P.; Bessis, R.; Sbaghi, M.; Meunier, P.; Trollat, P. Resveratrol content of wines of different ages: Relationship with fungal disease pressure in the vineyard. Am. J. Enol. Vitic., 1995, 46(1), 86153550.
[24]
Eckermann, C.; Matthes, B.; Nimtz, M.; Reiser, V.; Lederer, B.; Böger, P.; Schröder, J. Covalent binding of chloroacetamide herbicides to the active site cysteine of plant type III polyketide synthases. Phytochemistry, 2003, 64(6), 1045-1054.
[http://dx.doi.org/10.1016/S0031-9422(03)00516-8] [PMID: 14568070]
[25]
Chao, J.; Li, H.; Cheng, K.W.; Yu, M.S.; Chang, R.C.C.; Wang, M. Protective effects of pinostilbene, a resveratrol methylated derivative, against 6-hydroxydopamine-induced neurotoxicity in SH-SY5Y cells. J. Nutr. Biochem., 2010, 21(6), 482-489.
[http://dx.doi.org/10.1016/j.jnutbio.2009.02.004] [PMID: 19443200]
[26]
Yang, L.M.; Lin, S.J.; Hsu, F.L.; Yang, T.H. Antitumor agents. Part 3: Synthesis and cytotoxicity of new trans -Stilbene benzenesulfonamide derivatives. Bioorg. Med. Chem. Lett., 2002, 12(7), 1013-1015.
[http://dx.doi.org/10.1016/S0960-894X(02)00092-6] [PMID: 11909706]
[27]
Cardile, V.; Lombardo, L.; Spatafora, C.; Tringali, C. Chemo-enzymatic synthesis and cell-growth inhibition activity of resveratrol analogues. Bioorg. Chem., 2005, 33(1), 22-33.
[http://dx.doi.org/10.1016/j.bioorg.2004.08.003] [PMID: 15668180]
[28]
Burkhardt, S.; Reiter, R.J.; Tan, D.X.; Hardeland, R.; Cabrera, J.; Karbownik, M. DNA oxidatively damaged by chromium(III) and H2O2 is protected by the antioxidants melatonin, N1-acetyl-N2-formyl-5-methoxykynuramine, resveratrol and uric acid. Int. J. Biochem. Cell Biol., 2001, 33(8), 775-783.
[http://dx.doi.org/10.1016/S1357-2725(01)00052-8] [PMID: 11404181]
[29]
Bhat, K.P.L.; Pezzuto, J.M. Cancer chemopreventive activity of resveratrol. Ann. N. Y. Acad. Sci., 2002, 957(1), 210-229.
[http://dx.doi.org/10.1111/j.1749-6632.2002.tb02918.x] [PMID: 12074974]
[30]
Wang, Z.; Wei, P.; Wang, L.; Wang, Q. Design, synthesis, and anti-Tobacco Mosaic Virus (TMV) activity of phenanthroindolizidines and their analogues. J. Agric. Food Chem., 2012, 60(41), 10212-10219.
[http://dx.doi.org/10.1021/jf303550a] [PMID: 23035814]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy