{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T16:00:42Z","timestamp":1785081642819,"version":"3.55.0"},"reference-count":26,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82473967"],"award-info":[{"award-number":["82473967"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82273969"],"award-info":[{"award-number":["82273969"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry &amp; Biodiversity"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Although strategies combining multidrug resistance (MDR) reversal agents with chemotherapeutic drugs have demonstrated efficacy in clinical practice, their widespread application remains limited by potential toxicity. Natural thiazole\u2010containing macrocycles have displayed promising MDR reversal potential. However, the 18\u2010membered macrocycles bistratamides, despite their structural similarity to the known MDR reversal agent dendroamide A, remain unexplored regarding potential roles as MDR reversal agents and their molecular targets. In this study, we report the synthesis and initial discovery of bistratamides as potential MDR reversal agents. Structure\u2013activity relationship analysis revealed that the oxazoline or oxazole motifs embedded within the macrocyclic framework are essential for MDR reversal activity in bistratamides. The oxazoline\u2010containing bistratamide derivative\n                    <jats:bold>15<\/jats:bold>\n                    demonstrated the greatest synergistic anticancer effect among the examined compounds, exhibiting &gt; three\u2010fold greater activity than verapamil (VRP) with no observable toxicity in KBV cells and normal human podocytes. The MDR reversal effect of\n                    <jats:bold>15<\/jats:bold>\n                    in combination with paclitaxel was further validated through combination assays and flow cytometry. Subsequent rhodamine 123 (Rh123) accumulation assays and western blotting confirmed that\n                    <jats:bold>15\u00a0<\/jats:bold>\n                    exerts its MDR reversal activity by inhibiting P\u2010gp efflux function rather than affecting its expression. Our findings suggest that\n                    <jats:bold>15<\/jats:bold>\n                    represents a promising starting point for the development of novel chemosensitizing agents.\n                  <\/jats:p>","DOI":"10.1002\/cbdv.71317","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T06:53:26Z","timestamp":1778655206000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Discovery of Bistratamides as Efficacious Reversers of P\u2010Glycoprotein\u2010Mediated Multidrug Resistance"],"prefix":"10.1002","volume":"23","author":[{"given":"Ke","family":"Wang","sequence":"first","affiliation":[{"name":"Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education Yantai University  Yantai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sihan","family":"Qiang","sequence":"additional","affiliation":[{"name":"School of Chemistry and Chemical Engineering Yantai University  Yantai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziqiang","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Chemistry and Chemical Engineering Yantai University  Yantai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanshan","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education Yantai University  Yantai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunchang","family":"Yin","sequence":"additional","affiliation":[{"name":"School of Chemistry and Chemical Engineering Yantai University  Yantai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zongliang","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education Yantai University  Yantai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Yu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education Yantai University  Yantai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huili","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education Yantai University  Yantai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1513-8638","authenticated-orcid":false,"given":"Yi","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Chemistry and Chemical Engineering Yantai University  Yantai 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