{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T02:30:26Z","timestamp":1771036226023,"version":"3.50.1"},"reference-count":55,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2021,11,18]],"date-time":"2021-11-18T00:00:00Z","timestamp":1637193600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Council of Thailand and Health Systems Research Institute (HSRI),","award":["62-090"],"award-info":[{"award-number":["62-090"]}]},{"name":"Ratchadapisek sompotch endowment fund, Faculty of Medicine, Chulalongkorn University,","award":["MF-3\/62"],"award-info":[{"award-number":["MF-3\/62"]}]},{"name":"Ratchadapisek Somphot fund for Postdoctoral Fellowship, Chulalongkorn University.","award":["none"],"award-info":[{"award-number":["none"]}]},{"name":"CREST JST, Japan","award":["JP20338388"],"award-info":[{"award-number":["JP20338388"]}]},{"name":"a high-performance computing infrastructure project","award":["hp200157"],"award-info":[{"award-number":["hp200157"]}]},{"name":"AMED, Japan","award":["JP21ae0101047h0001"],"award-info":[{"award-number":["JP21ae0101047h0001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>A flavonoid is a versatile core structure with various cellular, immunological, and pharmacological effects. Recently, flavones have shown anti-dengue activities by interfering with viral translation and replication. However, the molecular target is still elusive. Here we chemically modified apigenin by adding an alkyne moiety into the B-ring hydroxyl group. The alkyne serves as a chemical tag for the alkyne-azide cycloaddition reaction for subcellular visualization. The compound located at the perinuclear region at 1 and 6 h after infection. Interestingly, the compound signal started shifting to vesicle-like structures at 6 h and accumulated at 24 and 48 h after infection. Moreover, the compound treatment in dengue-infected cells showed that the compound restricted the viral protein inside the vesicles, especially at 48 h. As a result, the dengue envelope proteins spread throughout the cells. The alkyne-tagged apigenin showed a more potent efficacy at the EC50 of 2.36 \u00b1 0.22, and 10.55 \u00b1 3.37 \u00b5M, respectively, while the cytotoxicities were similar to the original apigenin at the CC50 of 70.34 \u00b1 11.79, and 82.82 \u00b1 11.68 \u00b5M, respectively. Molecular docking confirmed the apigenin binding to the previously reported target, ribosomal protein S9, at two binding sites. The network analysis, homopharma, and molecular docking revealed that the estrogen receptor 1 and viral NS1 were potential targets at the late infection stage. The interactions could attenuate dengue productivity by interfering with viral translation and suppressing the viral proteins from trafficking to the cell surface.<\/jats:p>","DOI":"10.3390\/molecules26226967","type":"journal-article","created":{"date-parts":[[2021,11,19]],"date-time":"2021-11-19T02:43:09Z","timestamp":1637289789000},"page":"6967","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Alkyne-Tagged Apigenin, a Chemical Tool to Navigate Potential Targets of Flavonoid Anti-Dengue Leads"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8501-3844","authenticated-orcid":false,"given":"Kowit","family":"Hengphasatporn","sequence":"first","affiliation":[{"name":"Center for Computational Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benyapa","family":"Kaewmalai","sequence":"additional","affiliation":[{"name":"Applied Medical Virology Research Unit, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"},{"name":"Interdisciplinary Program in Microbiology, Graduate School, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Somruedee","family":"Jansongsaeng","sequence":"additional","affiliation":[{"name":"Center of Excellence for Natural Product, Department of Chemistry, Faculty of Science, Chulalongkorn University, Pathumwan, Bangkok 10330, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6433-2691","authenticated-orcid":false,"given":"Vishnu Nayak","family":"Badavath","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":"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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7882-6262","authenticated-orcid":false,"given":"Thamonwan","family":"Chokmahasarn","sequence":"additional","affiliation":[{"name":"Center of Excellence for Natural Product, Department of Chemistry, Faculty of Science, Chulalongkorn University, Pathumwan, Bangkok 10330, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7236-0625","authenticated-orcid":false,"given":"Tanatorn","family":"Khotavivattana","sequence":"additional","affiliation":[{"name":"Center of Excellence for Natural Product, Department of Chemistry, Faculty of Science, Chulalongkorn University, Pathumwan, Bangkok 10330, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3219-6007","authenticated-orcid":false,"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":"Thanyada","family":"Rungrotmongkol","sequence":"additional","affiliation":[{"name":"Structural and Computational Biology Research Unit, Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand"},{"name":"Program in Bioinformatics and Computational Biology, Graduate School, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3631-3573","authenticated-orcid":false,"given":"Siwaporn","family":"Boonyasuppayakorn","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"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,18]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2009). 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