Biological activity and interaction mechanism of the diketopiperazine derivatives as tubulin polymerization inhibitors.

ABSTRACT: Microtubules are a favorable target for development of anticancer agents. In this study, the anti-proliferative activities of plinabulin and six diketopiperazine derivatives were evaluated against human lung cancer cell line NCI-H460 and human pancreatic cancer cell line BxPC-3. The inhibition activities on these microtubules were assessed by tubulin polymerization and immunofluorescence assays. To gain insight into the interaction mechanism of the derivatives and tubulin, a molecular dynamics simulation was performed. We discovered that the diketopiperazine derivatives could prevent tubulin assembly through conformational changes. Molecular Mechanics/Poisson-Boltzmann Surface Area (MM-PBSA) calculations showed that the trend of the binding free energies of these inhibitors was in agreemen

SUBMITTER: Tian Z 

PROVIDER: S-EPMC9076956 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature