{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T12:28:44Z","timestamp":1753878524328,"version":"3.41.2"},"reference-count":21,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T00:00:00Z","timestamp":1748304000000},"content-version":"vor","delay-in-days":26,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Urolithin A (UA) is a dibenzo[<jats:italic>b,d<\/jats:italic>]pyran\u20106\u2010one polyhydroxy derivative produced as intestinal microbe metabolize ellagitannin and ellagic acid. Because of its superior anti\u2010inflammatory and antioxidant effects, it can cure neuronal damage in a variety of ways and play a neuroprotective role. More and more research has revealed that UA is a potential medicine for the treatment of neurodegenerative diseases. Due to UA source limitations, it is insufficient to achieve disease treatment concentrations, and the activity of UA inhibiting PDE2 needs further enhancement. As a result, we used UA as the parent nucleus structure, independently designed and used Discovery Studio software to assist in the structural design and molecular docking screening of the compounds, and tested the in\u00a0vitro enzyme activity of the synthesized compounds, hoping to obtain UA\u2010based PDE2 inhibitors. The IC<jats:sub>50<\/jats:sub> of 6\u201318, 6\u201319, 6\u201320, 6\u201322, and 6\u201329 were 0.62, 0.85, 1.51, 1.09, and 1.58\u2009\u03bcM, respectively. In this study, UA derivatives that can bind to the crystal structure of PDE2 protein 4HTX were proposed, which laid a groundwork for further structural modification, lead design, and development of small molecule inhibitors with inhibitory activity of PDE2.<\/jats:p>","DOI":"10.1111\/cbdd.70119","type":"journal-article","created":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T05:22:01Z","timestamp":1748409721000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Design, Synthesis, and Biological Activity of 8\u2010Hydroxyurolithin A Class <scp>PDE2<\/scp> Inhibitors"],"prefix":"10.1111","volume":"105","author":[{"given":"Qiulin","family":"Hu","sequence":"first","affiliation":[{"name":"School of Pharmacy and School of Biological and Food Engineering Changzhou University  Changzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Long","family":"Tang","sequence":"additional","affiliation":[{"name":"School of Pharmacy and School of Biological and Food Engineering Changzhou University  Changzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongqiu","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Pharmacy and School of Biological and Food Engineering Changzhou University  Changzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fen","family":"Yan","sequence":"additional","affiliation":[{"name":"School of Pharmacy and School of Biological and Food Engineering Changzhou University  Changzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guoqiang","family":"Song","sequence":"additional","affiliation":[{"name":"School of Pharmacy and School of Biological and Food Engineering Changzhou University  Changzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoqing","family":"Feng","sequence":"additional","affiliation":[{"name":"School of Pharmacy and School of Biological and Food Engineering Changzhou University  Changzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,5,27]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.7b01922"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2021.03.002"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2004.10.004"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox9020177"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph14010061"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6603(00)65001-8"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/jf402498b"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0049-3848(90)90276-I"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/jp8082612"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nlm.2014.10.011"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-022-00756-z"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-020-0593-1"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.5582\/ddt.2022.01039"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.3c01088"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21207462"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11101-016-9459-z"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.1c00692"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.0c02026"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.7b03285"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.3c01062"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja404449g"}],"container-title":["Chemical Biology &amp; 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