Development and Biological Evaluation of a Photoactivatable Small Molecule Microtubule-Targeting Agent

Alexander Döbber, Athena F. Phoa, Ramzi H. Abbassi, Brett W. Stringer, Bryan W. Day, Terrance G. Johns, Mohammed Abadleh, Christian Peifer, Lenka Munoz

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)


Photoremovable protecting groups added to bioactive molecules provide spatial and temporal control of the biological effects. We present synthesis and characterization of the first photoactivatable small-molecule tubulin inhibitor. By blocking the pharmacophoric OH group on compound 1 with photoremovable 4,5-dimethoxy-2-nitrobenzyl moiety we developed the photocaged prodrug 2 that had no effect in biological assays. Short UV light exposure of the derivative 2 or UV-irradiation of cells treated with 2 resulted in fast and potent inhibition of tubulin polymerization, attenuation of cell viability, and apoptotic cell death, implicating release of the parent active compound. This study validates for the first time the photoactivatable prodrug concept in the field of small molecule tubulin inhibitors. The caged derivative 2 represents a novel tool in antitubulin approaches.

Original languageEnglish
Pages (from-to)395-400
Number of pages6
JournalACS Medicinal Chemistry Letters
Issue number4
Publication statusPublished - 15 Mar 2017
Externally publishedYes


  • glioblastoma
  • Photoactivatable caged prodrug
  • tubulin inhibitor


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