Potent hemithioindigo-based antimitotics photocontrol the microtubule cytoskeleton in cellulo

• Alexander Sailer,
• Franziska Ermer,
• Yvonne Kraus,
• Rebekkah Bingham,
• Ferdinand H. Lutter,
• Julia Ahlfeld and
• Oliver Thorn-Seshold

Beilstein J. Org. Chem. 2020, 16, 125–134, doi:10.3762/bjoc.16.14

• photopharmaceutical antimitotics in a series of cell-free and cellular assays, and allowed robust photocontrol over tubulin polymerisation, microtubule (MT) network structure, cell cycle, and cell survival. Conclusions: HITubs represent a powerful addition to the growing toolbox of photopharmaceutical reagents for MT

• addressable by photopharmacology. Keywords: antimitotics; cytoskeleton; hemithioindigo; photopharmacology; photoswitch; Introduction The cytoskeletal scaffolding protein tubulin, a heterodimer consisting of α and β subunits, each of various isotypes, reversibly assembles into giant non-covalent polymeric

• developed HTI-based antimitotics with cytotoxic potencies in the low micromolar range (Figure 1a) [18]. In this work, we wished to enhance the bioactivity of the distinctive dark-active HTI-based tubulin-binding antimitotics while retaining the benefits of the HTI scaffold, namely robust, fatigue-resistant