{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T17:42:13Z","timestamp":1775238133439,"version":"3.50.1"},"reference-count":45,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,2,9]],"date-time":"2022-02-09T00:00:00Z","timestamp":1644364800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Shenzhen Bay Laboratory Start-up Fundation","award":["21230071"],"award-info":[{"award-number":["21230071"]}]},{"name":"the foundation by RFBR and NSFC","award":["20-53-55001"],"award-info":[{"award-number":["20-53-55001"]}]},{"name":"International Cooperation and Exchange Program of China","award":["82161148006"],"award-info":[{"award-number":["82161148006"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["21877007, 82130100"],"award-info":[{"award-number":["21877007, 82130100"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Betulinic acid (BA) and its derivatives exhibit a variety of biological activities, especially their anti-HIV-1 activity, but generally have only modest inhibitory potency against influenza virus. The entry of influenza virus into host cells can be competitively inhibited by multivalent derivatives targeting hemagglutinin. In this study, a series of hexa-, hepta- and octavalent BA derivatives based on \u03b1-, \u03b2- and \u03b3-cyclodextrin scaffolds, respectively, with varying lengths of flexible oligo(ethylene glycol) linkers was designed and synthesized using a microwave-assisted copper-catalyzed 1,3-dipolar cycloaddition reaction. The generated BA-cyclodextrin conjugates were tested for their in vitro activity against influenza A\/WSN\/33 (H1N1) virus and cytotoxicity. Among the tested compounds, 58, 80 and 82 showed slight cytotoxicity to Madin-Darby canine kidney cells with viabilities ranging from 64 to 68% at a high concentration of 100 \u03bcM. Four conjugates 51 and 69\u201371 showed significant inhibitory effects on influenza infection with half maximal inhibitory concentration values of 5.20, 9.82, 7.48 and 7.59 \u03bcM, respectively. The structure-activity relationships of multivalent BA-cyclodextrin conjugates were discussed, highlighting that multivalent BA derivatives may be potential antiviral agents against influenza infection.<\/jats:p>","DOI":"10.3390\/molecules27041163","type":"journal-article","created":{"date-parts":[[2022,2,9]],"date-time":"2022-02-09T21:22:15Z","timestamp":1644441735000},"page":"1163","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Facial Synthesis and Bioevaluation of Well-Defined OEGylated Betulinic Acid-Cyclodextrin Conjugates for Inhibition of Influenza Infection"],"prefix":"10.3390","volume":"27","author":[{"given":"Yingying","family":"Chen","sequence":"first","affiliation":[{"name":"State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinchen","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinyuan","family":"Ma","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuobin","family":"Liang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qianqian","family":"Gao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena V.","family":"Tretyakova","sequence":"additional","affiliation":[{"name":"Ufa Institute of Chemistry of the Ufa Federal Research Centre of the Russian Academy of Sciences, 71 Prospect Oktyabrya, 450054 Ufa, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8493-5812","authenticated-orcid":false,"given":"Yongmin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, CNRS, Institut Parisien de Chimie Mol\u00e9culaire, UMR 8232, 4 Place Jussieu, 75005 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Demin","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China"},{"name":"Shenzhen Bay Laboratory, Institute of Chemical Biology, Shenzhen 518132, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6852-9504","authenticated-orcid":false,"given":"Sulong","family":"Xiao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"E1","DOI":"10.1097\/CCM.0b013e3181cbaf34","article-title":"Influenza epidemiology-past, present, and future","volume":"38","author":"Rubinstein","year":"2010","journal-title":"Crit. 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