Synthesis and evaluation of selenium-containing indole chalcone and diarylketone derivatives as tubulin polymerization inhibition agents

Abstract

Sixteen new selenium-containing indole chalcone and diarylketone derivatives were synthesized and evaluated as tubulin polymerization inhibitors. Among them, compound 25b exhibited the most potent antiproliferative activities against six human cancer cell lines with IC₅₀ values of 0.004–0.022 μM. A microtubule dynamics assay and an immunofluorescence assay confirmed that 25b could effectively inhibit tubulin polymerization (IC₅₀ = 2.1 ± 0.27 μM). Further cellular mechanism studies revealed that 25b induced G2/M phase arrest, which was further evidenced by the decrease in the mitochondrial membrane potential (MMP).