Dibromopinocembrin and Dibromopinostrobin Are Potential Anti-Dengue Leads with Mild Animal Toxicity

被引:19
作者
Boonyasuppayakorn, Siwaporn [1 ]
Saelee, Thanaphon [1 ]
Visitchanakun, Peerapat [2 ,3 ]
Leelahavanichkul, Asada [3 ]
Hengphasatporn, Kowit [4 ]
Shigeta, Yasuteru [4 ]
Huynh, Thao Nguyen Thanh [5 ]
Chu, Justin Jang Hann [6 ]
Rungrotmongkol, Thanyada [7 ,8 ]
Chavasiri, Warinthorn [5 ]
机构
[1] Chulalongkorn Univ, Fac Med, Dept Microbiol, Appl Med Virol Res Unit, Bangkok 10330, Thailand
[2] Chulalongkorn Univ, Grad Sch, Interdisciplinary Program Microbiol, Bangkok 10330, Thailand
[3] Chulalongkorn Univ, Fac Med, Dept Microbiol, Translat Res Inflammat & Immunol Res Unit, Bangkok 10330, Thailand
[4] Univ Tsukuba, Ctr Computat Sci, 1-1-1 Tennodai, Tsukuba, Ibaraki 3058577, Japan
[5] Chulalongkorn Univ, Fac Sci, Ctr Excellence Nat Prod Chem, Dept Chem, Bangkok 10330, Thailand
[6] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Microbiol & Immunol, Lab Mol RNA Virol & Antiviral Strategies, Singapore 117545, Singapore
[7] Chulalongkorn Univ, Grad Sch, Program Bioinformat & Computat Biol, Bangkok 10330, Thailand
[8] Chulalongkorn Univ, Fac Sci, Dept Biochem, Biocatalyst & Environm Biotechnol Res Unit, Bangkok 10330, Thailand
关键词
dengue virus; flavanone; flavonoid; antiviral drug; dengue methyltransferase; drug discovery; pinocembrin; pinostrobin; ANTIVIRAL ACTIVITY; VIRUS-REPLICATION; BIOAVAILABILITY; TYPE-2; METABOLISM; ABSORPTION; FLAVANONES; INHIBITORS; DISCOVERY;
D O I
10.3390/molecules25184154
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Dengue infection is one of the most deleterious public health concerns for two-billion world population being at risk. Plasma leakage, hemorrhage, and shock in severe cases were caused by immunological derangement from secondary heterotypic infection. Flavanone, commonly found in medicinal plants, previously showed potential as anti-dengue inhibitors for its direct antiviral effects and suppressing the pro-inflammatory cytokine from dengue immunopathogenesis. Here, we chemically modified flavanones, pinocembrin and pinostrobin, by halogenation and characterized them as potential dengue 2 inhibitors and performed toxicity tests in human-derived cells and in vivo animal model. Dibromopinocembrin and dibromopinostrobin inhibited dengue serotype 2 at the EC(50)s of 2.0640 +/- 0.7537 and 5.8567 +/- 0.5074 mu M with at the CC(50)s of 67.2082 +/- 0.9731 and >100 mu M, respectively. Both of the compounds also showed minimal toxicity against adult C57BL/6 mice assessed by ALT and Cr levels in day one, three, and eight post-intravenous administration. Computational studies suggested the potential target be likely the NS5 methyltransferase at SAM-binding pocket. Taken together, these two brominated flavanones are potential leads for further drug discovery investigation.
引用
收藏
页数:16
相关论文
共 49 条
[1]   Functional entry of dengue virus into Aedes albopictus mosquito cells is dependent on clathrinmediated endocytosis [J].
Acosta, Eliana G. ;
Castilla, Viviana ;
Damonte, Elsa B. .
JOURNAL OF GENERAL VIROLOGY, 2008, 89 :474-484
[2]   Alkylated Flavanones from the Bark of Cryptocarya chartacea As Dengue Virus NS5 Polymerase Inhibitors [J].
Allard, Pierre-Marie ;
Dau, Elise Tran Huu ;
Eydoux, Cecilia ;
Guillemot, Jean-Claude ;
Dumontet, Vincent ;
Poullain, Cyril ;
Canard, Bruno ;
Gueritte, Francoise ;
Litaudon, Marc .
JOURNAL OF NATURAL PRODUCTS, 2011, 74 (11) :2446-2453
[3]  
Asakura H., 2018, Polyphenols: prevention and treatment of human disease, P279
[4]   Antiviral Activity of Faramea hyacinthina and Faramea truncata Leaves on Dengue Virus Type-2 and Their Major Compounds [J].
Barboza, Rodolfo S. ;
Valente, Ligia M. M. ;
Wolff, Thiago ;
Assuncao-Miranda, Iranaia ;
Neris, Romulo L. S. ;
Guimaraes-Andrade, Iris P. ;
Gomes, Mario .
CHEMISTRY & BIODIVERSITY, 2018, 15 (02)
[5]   Ecofriendly synthesis of halogenated flavonoids and evaluation of their antifungal activity [J].
Bernini, Roberta ;
Pasqualetti, Marcella ;
Provenzano, Gianfranco ;
Tempesta, Sabrina .
NEW JOURNAL OF CHEMISTRY, 2015, 39 (04) :2980-2987
[6]   Simplified dengue virus microwell plaque assay using an automated quantification program [J].
Boonyasuppayakorn, Siwaporn ;
Suroengrit, Aphinya ;
Srivarangkul, Pimsiri ;
Yuttithamnon, Wanchalerm ;
Pankaew, Saran ;
Saelee, Thanaphon ;
Prompetchara, Eakachai ;
Salakij, Saran ;
Bhattarakosol, Parvapan .
JOURNAL OF VIROLOGICAL METHODS, 2016, 237 :25-31
[7]  
Boonyasuppayakorn S, 2014, METHODS MOL BIOL, V1138, P361, DOI 10.1007/978-1-4939-0348-1_22
[8]  
Cassidy A., 2013, PHYTOCHEMICALS CLASS, P39, DOI [10.1016/B978-0-12-375083-9.00226-9, DOI 10.1016/B978-0-12-375083-9.00226-9]
[9]   Dogs demonstrate the existence of an epileptic seizure odour in humans [J].
Catala, Amelie ;
Grandgeorge, Marine ;
Schaff, Jean-Luc ;
Cousillas, Hugo ;
Hausberger, Martine ;
Cattet, Jennifer .
SCIENTIFIC REPORTS, 2019, 9 (1)
[10]   A point-charge force field for molecular mechanics simulations of proteins based on condensed-phase quantum mechanical calculations [J].
Duan, Y ;
Wu, C ;
Chowdhury, S ;
Lee, MC ;
Xiong, GM ;
Zhang, W ;
Yang, R ;
Cieplak, P ;
Luo, R ;
Lee, T ;
Caldwell, J ;
Wang, JM ;
Kollman, P .
JOURNAL OF COMPUTATIONAL CHEMISTRY, 2003, 24 (16) :1999-2012