biostudies-literatureda Silva Zanzarini IIntramural NIH HHSCNPqCAPES107283https://www.ebi.ac.uk/biostudies/studies/S-EPMC11069345biostudies-literatureUnknown146The breast cancer resistance protein (BCRP/ABCG2) transporter mediates the efflux of numerous antineoplastic drugs, playing a central role in multidrug resistance related to cancer. The absence of successful clinical trials using specific ABCG2 inhibitors reveals the urge to identify new compounds to attend this critical demand. In this work, a series of 13 magnolol derivatives was tested as ABCG2 inhibitors. Only two compounds, derivatives 10 and 11, showed partial and complete ABCG2 inhibitory effect, respectively. This inhibition was selective toward ABCG2, since none of the 13 compounds inhibited neither P-glycoprotein nor MRP1. Both inhibitors (10 and 11) were not transported by ABCG2 and demonstrated a low cytotoxic profile even at high concentrations (up to 100 µM). 11 emerged as thBioorganic chemistryMagnolol derivatives as specific and noncytotoxic inhibitors of breast cancer resistance protein (BCRP/ABCG2).PMC11069345Z01 BC010030Augusto Pastore MHenrique Kita Dda Silva Zanzarini IPicheth GValdameri GScheiffer GKaroline Dos Santos KPulvirenti LAmbudkar SVMuccilli Vde Paula Dutra JRotuno Moure VTringali CGomes de Moraes Rego FCardullo NfalseMagnolol derivatives as specific and noncytotoxic inhibitors of breast cancer resistance protein (BCRP/ABCG2).The breast cancer resistance protein (BCRP/ABCG2) transporter mediates the efflux of numerous antineoplastic drugs, playing a central role in multidrug resistance related to cancer. The absence of successful clinical trials using specific ABCG2 inhibitors reveals the urge to identify new compounds to attend this critical demand. In this work, a series of 13 magnolol derivatives was tested as ABCG2 inhibitors. Only two compounds, derivatives 10 and 11, showed partial and complete ABCG2 inhibitory effect, respectively. This inhibition was selective toward ABCG2, since none of the 13 compounds inhibited neither P-glycoprotein nor MRP1. Both inhibitors (10 and 11) were not transported by ABCG2 and demonstrated a low cytotoxic profile even at high concentrations (up to 100 µM). 11 emerged as th2024-01-01T00:00:00Z2024 May2026-06-02T20:44:41.899Z2026-04-20T03:10:42.46ZS-EPMC110693453851332410.1016/j.bioorg.2024.107283