Isoxazole-Based Compounds Targeting the Taxane-Binding Site of Tubulin.

ABSTRACT: Taxanes and other tubulin-targeting medications are essential for treating advanced malignancies, especially in patients undergoing less aggressive chemotherapy. However, their clinical efficacy is often limited by significant off-target toxicity and adverse side effects. In this study, the synthesis and characterisation of novel steroidal A-ring-fused isoxazoles, which were obtained through iodine-mediated oxidative cyclization of dihydrotestosterone (DHT)-derived α,β-unsaturated oximes, are reported. According to mechanistic studies, the most potent compounds induced mitotic arrest and disrupted cytoskeletal integrity at low micromolar concentrations. The lead compound, 2j, notably increased the rate of tubulin polymerisation in vitro and stabilised polymerised tubulin in the cells, lead

SUBMITTER: Perina M 

PROVIDER: S-EPMC12287683 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature