Abstract
Chrysin is a 5,7-dihydroxyflavone and was recently shown to potently inhibit enterovirus 71 (EV71) by suppressing viral 3C protease (3C(pro)) activity. In the current study, we investigated whether chrysin also shows antiviral activity against coxsackievirus B3 (CVB3), which belongs to the same genus (Enterovirus) as EV71, and assessed its ability to prevent the resulting acute pancreatitis and myocarditis. We found that chrysin showed antiviral activity against CVB3 at 10 μM, but exhibited mild cellular cytotoxicity at 50 μM, prompting us to synthesize derivatives of chrysin to increase the antiviral activity and reduce its cytotoxicity. Among four 4-substituted benzyl derivatives derived from C(5) benzyl-protected derivatives 7, 9-11 had significant antiviral activity and showed the most potent activity against CVB3 with low cytotoxicity in Vero cells. Intraperitoneal injection of CVB3 in BALB/c mice with 1×10(6) TCID50 (50% tissue culture infective dose) of CVB3 induced acute pancreatitis with ablation of acinar cells and increased serum CXCL1 levels, whereas the daily administration of 9 for 5 days significantly alleviated the pancreatic inflammation and reduced the elevation in serum CXCL1 levels. Collectively, we assessed...Continue Reading
References
Oct 25, 1995·Nucleic Acids Research·L D WoodA Richmond
Aug 15, 1997·Frontiers in Bioscience : a Journal and Virtual Library·A I Ramsingh
Aug 10, 2000·Journal of Medical Virology·S TracyC J Gauntt
Dec 2, 2006·Proceedings of the National Academy of Sciences of the United States of America·Carlos ZaragozaCharles J Lowenstein
Jan 6, 2009·Biological & Pharmaceutical Bulletin·Haiyan ZhuChenggang Huang
Jan 27, 2009·Vaccine·Jung-Hyun ParkJae-Hwan Nam
May 12, 2009·Journal of Clinical Immunology·Magnus LundgrenNils-Gunnar Ilbäck
May 20, 2009·Circulation·Toshitaka Yajima, Kirk U Knowlton
May 28, 2009·Phytotherapy Research : PTR·Paul SchnitzlerJürgen Reichling
Jun 18, 2010·Journal of Virology·Huifang M ZhangDecheng Yang
Sep 24, 2010·Journal of Virology·Christopher C KemballJ Lindsay Whitton
Nov 15, 2011·Archives of Virology·Steffi WilskyAndreas Henke
Feb 14, 2012·International Immunopharmacology·Young Han LeeSoon Young Shin
Mar 20, 2012·Cell Host & Microbe·Mehrdad AlirezaeiJ Lindsay Whitton
Nov 28, 2013·American Journal of Physiology. Endocrinology and Metabolism·Susan J BurkeJ Jason Collier
Mar 7, 2014·Biomolecules & Therapeutics·Jaehyoung SongHyun-Jeong Ko
Mar 7, 2014·PloS One·Jianmin WangQi Jin
Sep 17, 2014·Bioorganic & Medicinal Chemistry Letters·Phil Jun LeeHong Pyo Kim
Citations
Sep 16, 2017·Journal of Natural Medicines·Ninh Khac BanSeung Hyun Kim
Apr 26, 2018·Mini Reviews in Medicinal Chemistry·Yang LiYunmei Liu
Nov 2, 2019·Science Translational Medicine·Saravanan GunaseelanJustin Jang Hann Chu
May 11, 2017·Oncotarget·Eun-Hye HongHyun-Jeong Ko
May 27, 2017·Archives of Virology·Hovakim ZakaryanKeivan Zandi
Oct 21, 2020·Scientific Reports·Anamika BasuUjjwal Maulik
Nov 4, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Mohammad A I Al-HatamlehRohimah Mohamud
Nov 20, 2020·Animal Cells and Systems·Jae-Seung HongHong-Won Suh
Jul 3, 2021·Nutrients·Monika Stompor-GorącyMaciej Machaczka
Aug 11, 2021·Viruses·Seong-Ryeol KimHyun-Jeong Ko
Dec 13, 2018·Journal of Natural Products·Eun-Sun KimHyoungsu Kim