{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T04:03:31Z","timestamp":1769573011722,"version":"3.49.0"},"reference-count":25,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Science and Technology Department of Guizhou Province","award":["[2024]015"],"award-info":[{"award-number":["[2024]015"]}]},{"name":"Science and Technology Department of Guizhou Province","award":["[2026(341)]"],"award-info":[{"award-number":["[2026(341)]"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Non-small-cell lung cancer (NSCLC) is one of the most prevalent cancer types and accounts for the majority of cancer-related deaths worldwide. Tanshinone and its derivatives exhibit diverse biological activities, and their prominent antitumor potential has been well documented. In this study, we rationally designed a series of tanshinone derivatives with a scaffold-hopping strategy. Thirty-five tanshinone derivatives were synthesized, and their cytotoxic activities against the NSCLC cell lines A549 and H838 were investigated. Concurrently, their safety profile was assessed in BEAS-2B cells. The results showed that compounds S2-1, S2-4, and S2-8 exhibited superior inhibitory activity against A549 cells compared with the positive control, \u03b2-lapachone. Meanwhile, compounds S2-1, S2-3, S2-4, S2-8, S2-13, and S2-14 exhibited similar or increased antiproliferation activity against H838 cells. Compounds S2-4 (0.58 \u00b1 0.07 \u03bcM) and S2-8 (0.42 \u00b1 0.04 \u03bcM) demonstrated the greatest potency towards H838 cells; compounds S2-13 (1.28 \u00b1 0.13 \u03bcM) and S2-14 (1.80 \u00b1 0.24 \u03bcM) exhibited potent and selective activity towards H838 cells. Molecular docking studies of S2-4\/NLRP3 and S2-14\/STAT3, combined with the structure\u2013activity relationship (SAR) analysis, indicated that the benzofuran core containing an ortho-quinone, along with an amide linkage and a 1,2,3-triazole group introduced at the C-2 position of the furan ring, is an effective chemical scaffold for enhancing the anti-NSCLC activity of tanshinone derivatives.<\/jats:p>","DOI":"10.3390\/molecules31030446","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T15:41:56Z","timestamp":1769528516000},"page":"446","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Development of a Series of Tanshinone Derivatives Through Scaffold Hopping for Treating Non-Small-Cell Lung Cancer (NSCLC)"],"prefix":"10.3390","volume":"31","author":[{"given":"Lan-Xin","family":"Zhou","sequence":"first","affiliation":[{"name":"State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Guizhou Provincial Key Laboratory of Innovation and Manufacturing for Pharmaceuticals, Guizhou Medical University, Guiyang 550004, China"},{"name":"Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528400, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zheng-Yu","family":"Shu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Guizhou Provincial Key Laboratory of Innovation and Manufacturing for Pharmaceuticals, Guizhou Medical University, Guiyang 550004, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heng","family":"Li","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Zhong","sequence":"additional","affiliation":[{"name":"Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528400, China"},{"name":"Guangzhou University of Chinese Medicine, Guangzhou 510006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dou-Nan","family":"Xu","sequence":"additional","affiliation":[{"name":"Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528400, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Tang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Guizhou Provincial Key Laboratory of Innovation and Manufacturing for Pharmaceuticals, Guizhou Medical University, Guiyang 550004, China"},{"name":"Key Laboratory for Cancer Prevention and Treatment of Guizhou Province, Guiyang 550004, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chu-Jiao","family":"Hu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Guizhou Provincial Key Laboratory of Innovation and Manufacturing for Pharmaceuticals, Guizhou Medical University, Guiyang 550004, China"},{"name":"Key Laboratory for Cancer Prevention and Treatment of Guizhou Province, Guiyang 550004, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng","family":"Luo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Guizhou Provincial Key Laboratory of Innovation and Manufacturing for Pharmaceuticals, Guizhou Medical University, Guiyang 550004, China"},{"name":"Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528400, China"},{"name":"School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China"},{"name":"Guangzhou University of Chinese Medicine, Guangzhou 510006, China"},{"name":"Key Laboratory for Cancer Prevention and Treatment of Guizhou Province, Guiyang 550004, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huan","family":"Xiong","sequence":"additional","affiliation":[{"name":"Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528400, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2946","DOI":"10.1021\/acs.jmedchem.2c01967","article-title":"Scaffold Hybrid of the Natural Product Tanshinone I with Piperidine for 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