{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T09:06:17Z","timestamp":1784106377834,"version":"3.55.0"},"reference-count":46,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T00:00:00Z","timestamp":1783209600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T00:00:00Z","timestamp":1783209600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"NKRDPC","doi-asserted-by":"publisher","award":["2023YFD1800800"],"award-info":[{"award-number":["2023YFD1800800"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32473084"],"award-info":[{"award-number":["32473084"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U22A20518"],"award-info":[{"award-number":["U22A20518"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2026,7,14]]},"abstract":"<jats:p>\n                    Methicillin\u2010resistant\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    (MRSA) remains a major global health threat, driving demand for antibacterial agents with robust efficacy and low propensity for resistance. The natural xanthone \u03b1\u2010mangostin (\u03b1\u2010MG) shows potent anti\u2010MRSA activity via membrane disruption, but its high hydrophobicity and hemolytic liability limit therapeutic potential. Here, we designed and synthesized a focused series of C6\u2010\n                    <jats:italic>O<\/jats:italic>\n                    \u2010glycosylated \u03b1\u2010MG derivatives (\n                    <jats:bold>Y\u20101\u2013Y\u201015<\/jats:bold>\n                    ) bearing structurally diverse mono\u2010 and disaccharides to tune amphiphilicity and improve bacterial\u2010versus\u2010host selectivity. Among them,\n                    <jats:bold>Y\u20103<\/jats:bold>\n                    (\n                    <jats:italic>L<\/jats:italic>\n                    \u2010gulose conjugate) retained strong activity against both methicillin\u2010susceptible\n                    <jats:italic>S. aureus<\/jats:italic>\n                    and MRSA (MIC\u2009=\u20092\u2009\u03bcg\/mL), while markedly reducing red blood cell lysis (HC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u200948.20\u2009\u03bcg\/mL) and improving the selectivity index (SI\u2009=\u200924.10). Mechanistic assays showed that\n                    <jats:bold>Y\u20103<\/jats:bold>\n                    rapidly permeabilized and depolarized bacterial membranes. In phospholipid antagonism experiments, anionic bacterial lipids (cardiolipin and phosphatidylglycerol) reduced\n                    <jats:bold>Y\u20103<\/jats:bold>\n                    activity more strongly than phosphatidylcholine, supporting preferential interaction with bacterial\u2010type membranes. In a murine MRSA wound infection model, topical\n                    <jats:bold>Y\u20103<\/jats:bold>\n                    reduced bacterial burden and accelerated wound healing compared with the vehicle and \u03b1\u2010MG. Together, this study identifies C6 glycosylation as a practical strategy to decouple the antibacterial efficacy of \u03b1\u2010MG from host membrane toxicity and support\n                    <jats:bold>Y\u20103<\/jats:bold>\n                    as a lead for topical anti\u2010MRSA development.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.70366","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T06:27:14Z","timestamp":1783319234000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Synthesis and Biological Evaluation of C6\u2010\n                    <i>O<\/i>\n                    \u2010Glycosylated \u03b1\u2010Mangostin Derivatives Against Methicillin\u2010Resistant\n                    <i>Staphylococcus aureus<\/i>\n                    With Enhanced Bacterial Membrane Selectivity"],"prefix":"10.1002","volume":"21","author":[{"given":"Wenchong","family":"Ye","sequence":"first","affiliation":[{"name":"Shanghai Veterinary Research Institute Chinese Academy of Agricultural Sciences  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuangchuang","family":"Fan","sequence":"additional","affiliation":[{"name":"Shanghai Veterinary Research Institute Chinese Academy of Agricultural Sciences  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiantian","family":"Zhou","sequence":"additional","affiliation":[{"name":"Shanghai Veterinary Research Institute Chinese Academy of Agricultural Sciences  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyang","family":"Wang","sequence":"additional","affiliation":[{"name":"Shanghai Veterinary Research Institute Chinese Academy of Agricultural Sciences  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunmei","family":"Wang","sequence":"additional","affiliation":[{"name":"Shanghai Veterinary Research Institute Chinese Academy of Agricultural Sciences  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shanghai Veterinary Research Institute Chinese Academy of Agricultural Sciences  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5195-5059","authenticated-orcid":false,"given":"Shengyi","family":"Wang","sequence":"additional","affiliation":[{"name":"Lanzhou Institute of Husbandry and Pharmaceutical Sciences Chinese Academy of Agricultural Sciences  Lanzhou China"},{"name":"Key Lab of Veterinary Pharmaceutical Development of Ministry of Agriculture  Lanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3961-1816","authenticated-orcid":false,"given":"Wen","family":"Zhou","sequence":"additional","affiliation":[{"name":"Shanghai Veterinary Research Institute Chinese Academy of Agricultural Sciences  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,5]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2024.101178"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2024.01.004"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.adn1369"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201037310\u20105"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/smll.202304194"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2023.01.005"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.4c00436"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.4c01860"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.4c03167"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.3c02064"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2024.117187"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2025.109289"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.2c01583"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1039\/c8np00031j"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202100749"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010024\u201007530\u2010w"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics12020232"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2012.09.004"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5b01500"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2023.155069"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2023.115251"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202411923"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2023.117232"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph16030439"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1039\/d2np00089j"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2022.06.009"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1039\/d4sc08242g"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/chem.202403943"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.colsurfb.2021.112146"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcis.2022.02.120"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2022.898794"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.01631\u201024"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40580\u2010022\u201000339\u20101"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1039\/d3cc02320f"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/ardp.202400793"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adp9448"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201050453\u20103"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.01623\u201023"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2025.109108"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.20913"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph15050552"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.112670"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/1751\u20107915.70249"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.00191\u201024"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.5c14268"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioflm.2024.100224"}],"container-title":["ChemMedChem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.70366","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cmdc.70366","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.70366","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T08:3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