{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T13:03:08Z","timestamp":1773493388335,"version":"3.50.1"},"reference-count":30,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:00:00Z","timestamp":1760313600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:00:00Z","timestamp":1760313600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry &amp;amp; Biodiversity"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Invasive fungal infections have a high mortality rate, and the current antifungal arsenal is limited by toxicity, resistance, and the small number of available drugs. Polyalthic acid is a natural product with modest antifungal activity and low toxicity. Therefore, it is a suitable candidate for structural modification to enhance its antifungal activity. Six polyalthic acid analogs were synthesized, and their activity was tested against\n                    <jats:italic>Candida albicans<\/jats:italic>\n                    and\n                    <jats:italic>Cryptococcus neoformans<\/jats:italic>\n                    . The best compound was\n                    <jats:bold>2b<\/jats:bold>\n                    with MICs of 21.8 and 12.3\u00a0\u00b5g\/mL, respectively. We further investigated the mechanism of action of\n                    <jats:bold>2b<\/jats:bold>\n                    by assessing its effects on ROS production and plasma membrane integrity in\n                    <jats:italic>C. neoformans<\/jats:italic>\n                    . Intracellular ROS levels were measured using H\n                    <jats:sub>2<\/jats:sub>\n                    DCFH\u2010DA, while membrane integrity was evaluated using DAPI staining. A significant increase in ROS generation was detected at concentrations \u2265\u00a04\u00a0\u00b5g\/mL as early as 1\u00a0h after treatment. DAPI intensity and focal staining pattern were observed at all concentrations tested after 7.5\u00a0h of treatment. These findings indicated that the antifungal activity of\n                    <jats:bold>2b<\/jats:bold>\n                    involves reactive oxygen species production and disruption of membrane integrity. The current study supports\n                    <jats:bold>2b<\/jats:bold>\n                    as a potential lead compound for the development of new antifungal agents to address the limitations of current therapies.\n                  <\/jats:p>","DOI":"10.1002\/cbdv.202502678","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T05:02:12Z","timestamp":1760418132000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Antifungal Activity of Polyalthic Acid Analogs Against\n                    <i>Cryptococcus neoformans<\/i>\n                    Involves Production of Reactive Oxygen Species (ROS) and Disruption of Cell Membrane Integrity"],"prefix":"10.1002","volume":"22","author":[{"given":"Thomas A.","family":"Mennella","sequence":"first","affiliation":[{"name":"Department of Physical and Biological Sciences Western New England University  Springfield Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyung U.","family":"Hong","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Health Sciences Western New England University  Springfield Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joshua","family":"Bojito","sequence":"additional","affiliation":[{"name":"Department of Physical and Biological Sciences Western New England University  Springfield Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas R.","family":"Roche","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Health Sciences Western New England University  Springfield Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eun\u2010Jung","family":"Park","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Health Sciences Western New England University  Springfield Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ariana B.","family":"Souza","sequence":"additional","affiliation":[{"name":"N\u00facleo de Pesquisa em Ci\u00eancias Exatas e Tecnol\u00f3gicas Universidade De Franca  Franca Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rodrigo C. S.","family":"Veneziani","sequence":"additional","affiliation":[{"name":"N\u00facleo de Pesquisa em Ci\u00eancias Exatas e Tecnol\u00f3gicas Universidade De Franca  Franca Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S\u00e9rgio R.","family":"Ambr\u00f3sio","sequence":"additional","affiliation":[{"name":"N\u00facleo de Pesquisa em Ci\u00eancias Exatas e Tecnol\u00f3gicas Universidade De Franca  Franca Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jairo K.","family":"Bastos","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences of Ribeir\u00e3o Preto University of S\u00e3o Paulo  Ribeir\u00e3o Preto Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suresh","family":"Annam","sequence":"additional","affiliation":[{"name":"National Center for Natural Products Research, School of Pharmacy University of Mississippi University  Mississippi USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7678-1662","authenticated-orcid":false,"given":"Cassia S.","family":"Mizuno","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Health Sciences Western New England University  Springfield Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,10,13]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473\u20103099(23)00692\u20108"},{"key":"e_1_2_8_3_1","unstructured":"World Health Organization WHO Fungal Priority Pathogens List to Guide Research Development and Public Health Action 1st ed.(World Health Organization 2022)."},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.8.3264\u20103273.2005"},{"key":"e_1_2_8_5_1","unstructured":"www.cdc.gov."},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010020\u201063240\u2010z"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics9120877"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2023.115007"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s15010\u2010020\u201001475\u20108"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.2165\/00002018\u2010199005020\u201000003"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/jof10050334"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.10.030"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2018.11.029"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s43450\u2010020\u201000002\u2010y"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1177\/1934578X241282853"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2019.103560"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics12071202"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2015.10.062"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2009.11.064"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2012.11.006"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jnatprod.9b00305"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom5020318"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2023.1276406"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.115.179150"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00978\u201017"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/jof6040321"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.3109\/10520299509108199"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph20010027"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010023\u201029756\u2010w"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xpro.2023.102512"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/jpids\/piad014"}],"container-title":["Chemistry &amp; 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