Triethylated chromones with substituted naphthalenes as tubulin inhibitors.

ABSTRACT: Previously synthesized 2-(benzo[b]thiophene-3'-yl)-6,8,8-triethyldesmosdumotin B (1, TEDB-TB) and 2-(naphth-1'-yl)-6,8,8-triethyldesmosdumotin B (2) showed potent activity against multiple human tumor cell lines, including a multidrug-resistant (MDR) subline, by targeting spindle formation and/or the microtubule network. Consequently, ester analogues of hydroxylated naphthyl substituted TEBDs (3-5) were prepared and evaluated for their effects on tumor cell proliferation and on tubulin assembly. Among all new compounds, compound 6, a 4'-acetoxynaphthalen-1'-yl derivative, displayed the most potent antiproliferative activity (IC₅₀ 0.2-5.7μM). Selected analogues were confirmed to be tubulin assembly inhibitors in cell-free and cell-based assays using MDR tumor cells. The new analo

SUBMITTER: Nakagawa-Goto K 

PROVIDER: S-EPMC5079804 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature