{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T20:40:58Z","timestamp":1789504858965,"version":"build-2803163510"},"reference-count":32,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T00:00:00Z","timestamp":1748995200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Yunnan Province Agricultural Basic Research Joint Foundation","award":["202401BD070001-074"],"award-info":[{"award-number":["202401BD070001-074"]}]},{"name":"Yunnan Province Agricultural Basic Research Joint Foundation","award":["202501AT070141"],"award-info":[{"award-number":["202501AT070141"]}]},{"name":"Yunnan Provincial Basic Research Special Project\u2014General Project","award":["202401BD070001-074"],"award-info":[{"award-number":["202401BD070001-074"]}]},{"name":"Yunnan Provincial Basic Research Special Project\u2014General Project","award":["202501AT070141"],"award-info":[{"award-number":["202501AT070141"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The tetrahydro-\u03b2-carboline heterocycle is a privileged scaffold found in numerous natural products and bioactive drugs, demonstrating significant potential for cancer therapy. In this study, we designed and synthesized 33 novel tetrahydro-\u03b2-carboline derivatives (2\u201334) based on this core structure and evaluated their anticancer activity against human lung cancer (A549). Among them, compounds 8 and 16 exhibited potent cytotoxicity against A549 cells, effectively suppressing cell migration and colony formation. Mechanistic studies revealed that these compounds promoted apoptosis by upregulating pro-apoptotic Bax, downregulating anti-apoptotic Bcl-2, and activating caspase proteins. Molecular docking and dynamics simulations demonstrated that compounds 8 and 16 form stable complexes with the Eg5 protein through multiple hydrogen bonds, which was further validated by thermal shift assays. Collectively, these findings indicate that compounds 8 and 16 induce apoptosis in A549 cells by selectively targeting and stabilizing Eg5, highlighting their potential as lead candidates for lung cancer therapy.<\/jats:p>","DOI":"10.3390\/ijms26115396","type":"journal-article","created":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T10:10:16Z","timestamp":1749031816000},"page":"5396","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Antitumor Activity of Tetrahydro-\u03b2-carboline Derivatives via Inhibition of Kinesin Spindle Protein: Validation by Molecular Docking, Molecular Dynamics, and In Vitro Assays"],"prefix":"10.3390","volume":"26","author":[{"given":"Saizhen","family":"Guo","sequence":"first","affiliation":[{"name":"College of Science, Yunnan Agricultural University, Kunming 650201, China"},{"name":"College of Food Science and Technology, Yunnan Agricultural University, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Science, Yunnan Agricultural University, Kunming 650201, China"},{"name":"College of Food Science and Technology, Yunnan Agricultural University, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingyuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Science, Yunnan Agricultural University, Kunming 650201, China"},{"name":"College of Food Science and Technology, Yunnan Agricultural University, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjuan","family":"Yuan","sequence":"additional","affiliation":[{"name":"College of Science, Yunnan Agricultural University, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2367-3617","authenticated-orcid":false,"given":"Chengting","family":"Zi","sequence":"additional","affiliation":[{"name":"College of Food Science and Technology, Yunnan Agricultural University, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zemin","family":"Xiang","sequence":"additional","affiliation":[{"name":"College of Food Science and Technology, Yunnan Agricultural University, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongkai","family":"Xi","sequence":"additional","affiliation":[{"name":"College of Science, Yunnan Agricultural University, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1002\/jlcr.3804","article-title":"Radiolabeling and in vitro evaluation of a new 5-fluorouracil derivative with cell culture studies","volume":"62","author":"Ekinci","year":"2019","journal-title":"J. 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