{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T13:46:06Z","timestamp":1778075166332,"version":"3.51.4"},"reference-count":37,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T00:00:00Z","timestamp":1757894400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"specific research fund of The Innovation Platform for Academicians of Hainan Province","award":["YSPTZX202409"],"award-info":[{"award-number":["YSPTZX202409"]}]},{"name":"specific research fund of The Innovation Platform for Academicians of Hainan Province","award":["825RC780"],"award-info":[{"award-number":["825RC780"]}]},{"name":"specific research fund of The Innovation Platform for Academicians of Hainan Province","award":["KJRC2023D23"],"award-info":[{"award-number":["KJRC2023D23"]}]},{"name":"specific research fund of The Innovation Platform for Academicians of Hainan Province","award":["Hnky2024-34"],"award-info":[{"award-number":["Hnky2024-34"]}]},{"name":"Hainan Province High-level Talent special","award":["YSPTZX202409"],"award-info":[{"award-number":["YSPTZX202409"]}]},{"name":"Hainan Province High-level Talent special","award":["825RC780"],"award-info":[{"award-number":["825RC780"]}]},{"name":"Hainan Province High-level Talent special","award":["KJRC2023D23"],"award-info":[{"award-number":["KJRC2023D23"]}]},{"name":"Hainan Province High-level Talent special","award":["Hnky2024-34"],"award-info":[{"award-number":["Hnky2024-34"]}]},{"name":"Science and Technology Talent Innovation Project of Hainan Province","award":["YSPTZX202409"],"award-info":[{"award-number":["YSPTZX202409"]}]},{"name":"Science and Technology Talent Innovation Project of Hainan Province","award":["825RC780"],"award-info":[{"award-number":["825RC780"]}]},{"name":"Science and Technology Talent Innovation Project of Hainan Province","award":["KJRC2023D23"],"award-info":[{"award-number":["KJRC2023D23"]}]},{"name":"Science and Technology Talent Innovation Project of Hainan Province","award":["Hnky2024-34"],"award-info":[{"award-number":["Hnky2024-34"]}]},{"name":"The Education Department of Hainan Province","award":["YSPTZX202409"],"award-info":[{"award-number":["YSPTZX202409"]}]},{"name":"The Education Department of Hainan Province","award":["825RC780"],"award-info":[{"award-number":["825RC780"]}]},{"name":"The Education Department of Hainan Province","award":["KJRC2023D23"],"award-info":[{"award-number":["KJRC2023D23"]}]},{"name":"The Education Department of Hainan Province","award":["Hnky2024-34"],"award-info":[{"award-number":["Hnky2024-34"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Recent studies on brominated tyrosine-derived marine natural products have significantly expanded the library of known structures and revealed their potent and diverse antitumor mechanisms. Building upon our previous research on the natural product itampolin A isolated from marine sponges, we conducted structural optimizations and explored the structure\u2013-activity relationships (SARs) of novel scaffold derivatives concerning their inhibitory activities against lung cancer cells. In the present study, we further synthesized 15 novel derivatives, and compound 4l demonstrated selective anti-proliferative activity against gefitinib-resistant PC9\/GR cells, showing 4-fold greater potency compared to parental PC9 cells. Building on this finding, the present study aims to investigate the molecular mechanisms underlying the anti-proliferative effects of 4l in drug-resistant NSCLC models. Through cell cycle analysis, apoptosis assays, and signaling pathway evaluation, we seek to establish a theoretical foundation for developing novel therapeutic agents against chemotherapy-resistant lung cancer.<\/jats:p>","DOI":"10.3390\/md23090357","type":"journal-article","created":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T10:51:33Z","timestamp":1757933493000},"page":"357","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Design and Synthesis of Marine-Inspired Itampolin A Derivatives to Overcome Chemoresistance in NSCLC via Cholesterol Homeostasis Modulation"],"prefix":"10.3390","volume":"23","author":[{"given":"Hai-Ying","family":"Zhang","sequence":"first","affiliation":[{"name":"Engineering Research Center of Tropical Medicine Innovation and Transformation of Ministry of Education, School of Pharmacy, Hainan Medical University, Haikou 571199, China"},{"name":"Hainan Provincial Key Laboratory for Research and Development of Tropical Herbs, Haikou 571199, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shun-Chang","family":"Ji","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Tropical Medicine Innovation and Transformation of Ministry of Education, School of Pharmacy, Hainan Medical University, Haikou 571199, China"},{"name":"Hainan Provincial Key Laboratory for Research and Development of Tropical Herbs, Haikou 571199, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Si-Hua","family":"Xie","sequence":"additional","affiliation":[{"name":"School of Pharmacy, China Medical University, Shenyang 110122, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Chen","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Tropical Medicine Innovation and Transformation of Ministry of Education, School of Pharmacy, Hainan Medical University, Haikou 571199, China"},{"name":"Hainan Provincial Key Laboratory for Research and Development of Tropical Herbs, Haikou 571199, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cai-Xia","family":"Lin","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Tropical Medicine Innovation and Transformation of Ministry of Education, School of Pharmacy, Hainan Medical University, Haikou 571199, China"},{"name":"Hainan Provincial Key Laboratory for Research and Development of Tropical Herbs, Haikou 571199, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xu","family":"Huang","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Tropical Medicine Innovation and Transformation of Ministry of Education, School of Pharmacy, Hainan Medical University, Haikou 571199, China"},{"name":"School of Pharmacy, China Medical University, Shenyang 110122, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3921-9116","authenticated-orcid":false,"given":"Yi-Qiao","family":"Wang","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Tropical Medicine Innovation and Transformation of Ministry of Education, School of Pharmacy, Hainan Medical University, Haikou 571199, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing-Wei","family":"Liang","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Tropical Medicine Innovation and Transformation of Ministry of Education, School of Pharmacy, Hainan Medical University, Haikou 571199, China"},{"name":"Hainan Provincial Key Laboratory for Research and Development of Tropical Herbs, Haikou 571199, China"},{"name":"School of Pharmacy, China Medical University, Shenyang 110122, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Liu","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Tropical Medicine Innovation and Transformation of Ministry of Education, School of Pharmacy, Hainan Medical University, Haikou 571199, China"},{"name":"Hainan Provincial Key Laboratory for Research and Development of Tropical Herbs, Haikou 571199, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Yuan, Y., Lei, Y., Xu, M., Zhao, B., and Xu, S. 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