{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T06:43:02Z","timestamp":1769150582297,"version":"3.49.0"},"reference-count":49,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2020,9,11]],"date-time":"2020-09-11T00:00:00Z","timestamp":1599782400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ratchadapisek sompotch endowment fund, Faculty of Medicine, Chulalongkorn University","award":["MF-3\/62."],"award-info":[{"award-number":["MF-3\/62."]}]},{"name":"National Research Council of Thailand and Health Systems Research Institute (HSRI)","award":["62-090"],"award-info":[{"award-number":["62-090"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>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 EC50s of 2.0640 \u00b1 0.7537 and 5.8567 \u00b1 0.5074 \u00b5M with at the CC50s of 67.2082 \u00b1 0.9731 and &gt;100 \u00b5M, 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.<\/jats:p>","DOI":"10.3390\/molecules25184154","type":"journal-article","created":{"date-parts":[[2020,9,13]],"date-time":"2020-09-13T22:01:01Z","timestamp":1600034461000},"page":"4154","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Dibromopinocembrin and Dibromopinostrobin Are Potential Anti-Dengue Leads with Mild Animal Toxicity"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3631-3573","authenticated-orcid":false,"given":"Siwaporn","family":"Boonyasuppayakorn","sequence":"first","affiliation":[{"name":"Applied Medical Virology Research Unit, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thanaphon","family":"Saelee","sequence":"additional","affiliation":[{"name":"Applied Medical Virology Research Unit, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peerapat","family":"Visitchanakun","sequence":"additional","affiliation":[{"name":"Interdisciplinary Program in Microbiology, Graduate School, Chulalongkorn University, Bangkok 10330, Thailand"},{"name":"Translational Research in Inflammation and Immunology Research Unit, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asada","family":"Leelahavanichkul","sequence":"additional","affiliation":[{"name":"Translational Research in Inflammation and Immunology Research Unit, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8501-3844","authenticated-orcid":false,"given":"Kowit","family":"Hengphasatporn","sequence":"additional","affiliation":[{"name":"Center for Computational Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuteru","family":"Shigeta","sequence":"additional","affiliation":[{"name":"Center for Computational Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thao Nguyen Thanh","family":"Huynh","sequence":"additional","affiliation":[{"name":"Center of Excellence in Natural Products Chemistry, Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justin Jang Hann","family":"Chu","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular RNA Virology and Antiviral Strategies, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thanyada","family":"Rungrotmongkol","sequence":"additional","affiliation":[{"name":"Program in Bioinformatics and Computational Biology, Graduate School, Chulalongkorn University, Bangkok 10330, Thailand"},{"name":"Biocatalyst and Environmental Biotechnology Research Unit, Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Warinthorn","family":"Chavasiri","sequence":"additional","affiliation":[{"name":"Center of Excellence in Natural Products Chemistry, Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,11]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (WHO) (2020, June 25). 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