Concise synthesis and biological activity evaluation of novel pyrazinyl-aryl urea derivatives against several cancer cell lines, which can especially induce T24 apoptotic and necroptotic cell death.

ABSTRACT: Based on the structural modification of regorafenib, 28 pyrazinyl-aryl urea derivatives were synthesized and their in vitro antiproliferative activities were evaluated. Six compounds (5-16, 5-17, 5-18, 5-19, 5-22, and 5-23) exhibited favorable inhibitory activity against the human bladder cancer T24 cell line, and 5-23 demonstrated the strongest inhibitory activity (IC₅₀ = 4.58 ± 0.24 μM) with high selectivity. Compound 5-23 induced apoptosis in the low concentration range (≤7.5 μM) combined with shorter incubation time (≤10 h) via the activation of caspases, while high concentrations and prolonged incubation times led to necroptotic cell death by activating the RIPK1/RIPK3/MLKL signaling pathway. Induced apoptosis and necroptosis were closely associated with intra

SUBMITTER: Chen JN 

PROVIDER: S-EPMC8942210 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature