Novel Adamantane-Sclareol Hybrids Exploit ROS Vulnerability to Overcome Multidrug-Resistance in Glioblastoma Cells.

ABSTRACT: Multidrug resistance (MDR) presents a significant challenge in the treatment of glioblastoma. We evaluated six novel adamantane-sclareol hybrids that integrate a natural labdane diterpene scaffold with an adamantane moiety to address this issue. Compounds 2, 5, and 6 demonstrated the ability to bypass P-glycoprotein (P-gp)-mediated resistance in resistant U87-TxR cells and induced collateral sensitivity, with compound 2 exhibiting the highest selectivity for glioblastoma compared to normal glial cells. Mechanistic studies revealed that compounds 2 and 5 selectively triggered early apoptosis in MDR cells, significantly elevated levels of H₂O₂ and peroxynitrite, and disrupted mitochondrial membrane potential. Additionally, these

SUBMITTER: Lupsic E 

PROVIDER: S-EPMC12735718 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature