Discovery of Novel 4-Arylisochromenes as Anticancer Agents Inhibiting Tubulin Polymerization.

ABSTRACT: XJP-L (8), a derivative of the natural product (±)-7,8-dihydroxy-3-methylisochroman-4-one isolated from the peel of Musa sapien tum L., was found to exhibit weak inhibitory activity of tubulin polymerization (IC₅₀ = 10.6 μM) in our previous studies. Thus, a series of 4-arylisochromene derivatives were prepared by incorporating the trimethoxyphenyl moiety into 8, among which compound (±)-19b was identified as the most potent compound with IC₅₀ values ranging from 10 to 25 nM against a panel of cancer cell lines. Further mechanism studies demonstrated that (±)-19b disrupted the intracellular microtubule network, caused G2/M phase arrest, induced cell apoptosis, and depolarized mitochondria of K562 cells. Moreover, (±)-19b exhibi

SUBMITTER: Li W 

PROVIDER: S-EPMC6187416 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature