{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T15:07:21Z","timestamp":1783955241899,"version":"3.55.0"},"reference-count":29,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,7,31]],"date-time":"2024-07-31T00:00:00Z","timestamp":1722384000000},"content-version":"vor","delay-in-days":0,"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":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Inhibition of SIRT3 exhibited potency in triggering leukemic cell differentiation. In discovery of potent SIRT3 inhibitors for cancer differentiation therapy, structural modification was performed on the previously developed lead compound <jats:bold>P6<\/jats:bold>. A total of 33 compounds were designed and synthesized. In the enzyme inhibitory assay, several molecules <jats:bold>S18<\/jats:bold>, <jats:bold>S26<\/jats:bold>, <jats:bold>S27<\/jats:bold> and <jats:bold>T5<\/jats:bold> showed potent SIRT3 inhibitory activity with IC<jats:sub>50<\/jats:sub> value of 0.53, 1.86, 5.06, and 2.88\u2009\u03bcM, respectively. Moreover, the tested compounds exhibited SIRT3 inhibitory selectivity over SIRT1 and SIRT2. Compounds <jats:bold>S27<\/jats:bold> and <jats:bold>T5<\/jats:bold> were potent in inhibition the growth of MM1.S and RPMI\u20108226 cells in the in\u00a0vitro antiproliferative test. Significantly, representative compounds, especially <jats:bold>S27<\/jats:bold> and <jats:bold>T5<\/jats:bold>, promoted differentiation of tested MM cells in the cellular morphological evaluation, accompanied by increasing the expression of differentiation antigen CD49e and human immunoglobulin light chain lambda and kappa. Additionally, molecule <jats:bold>S18<\/jats:bold> without antiproliferative potency itself, showed significant inhibitory activity against growth factor IL\u20106 induced RPMI\u20108226 cell proliferation. Collectively, potent SIRT3 selective inhibitors with MM cell differentiation potency were developed for further discovery of anticancer drugs.<\/jats:p>","DOI":"10.1111\/cbdd.14595","type":"journal-article","created":{"date-parts":[[2024,8,1]],"date-time":"2024-08-01T03:36:12Z","timestamp":1722483372000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Structural modification of 2\u2010phenylquinoline\u20104\u2010carboxylic acid containing <scp>SIRT3<\/scp> inhibitors for the cancer differentiation therapy"],"prefix":"10.1111","volume":"104","author":[{"given":"Yanmei","family":"Du","sequence":"first","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy Shandong Second Medical University  Weifang Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, School of Pharmacy Shandong Second Medical University  Weifang Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihui","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Stomatology Shandong Second Medical University  Weifang Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyu","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, School of Pharmacy Shandong Second Medical University  Weifang Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangzhao","family":"Xu","sequence":"additional","affiliation":[{"name":"Harway Pharma Co., LTD.  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