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Natural compounds, prized for their structural complexity and diverse bioactivities, remain a valuable source for drug discovery. Shikonin (SHK), a naturally occurring naphthoquinone, has demonstrated potent anti\u2010tumor properties across various cancer types. This study synthesized a series of SHK derivatives via olefin metathesis to investigate the functional role of the isohexenyl side chain. Among the synthesized compounds,\n                    <jats:bold>S6<\/jats:bold>\n                    bearing a fluorophenyl group showed enhanced anti\u2010pancreatic cancer activity, achieving a 50% inhibitory concentration of 0.9 \u00b5M against AsPC\u20101 cells within 24 h. Mechanistic analysis showed that\n                    <jats:bold>S6<\/jats:bold>\n                    inhibited the AKT and mTOR signaling pathways, leading to excessive autophagy and significantly reducing the proliferation and migration of pancreatic cancer cells. In vivo assessments further demonstrated a dose\u2010dependent reduction in tumor volume following\n                    <jats:bold>S6<\/jats:bold>\n                    treatment, highlighting its potential as a promising candidate for pancreatic cancer therapy.\n                  <\/jats:p>","DOI":"10.1002\/cbdv.202500721","type":"journal-article","created":{"date-parts":[[2025,7,20]],"date-time":"2025-07-20T19:33:51Z","timestamp":1753040031000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Shikonin Derivative Induces Excessive Autophagy in Pancreatic Cancer Cells"],"prefix":"10.1002","volume":"22","author":[{"given":"Qixia","family":"Cao","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy Harbin Medical University  Harbin 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