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

• hemithioindigo-based indanone-like tubulin inhibitors (HITubs) and optimised their cellular potency as antimitotic photopharmaceuticals. These HITubs feature reliable and robust visible-light photoswitching and high fatigue resistance. The use of the hemithioindigo scaffold also permitted us to employ a para

• understanding MT biology; and optogenetic modifications of tubulin have never succeeded. Instead, studies of the roles of MTs in these processes overwhelmingly rely on small molecule tubulin inhibitors [1]. Due to the non-invasiveness and high spatiotemporal precision with which optical stimulation can be

• to assess the biological activity of HITubs in all cellular experiments shown in this work. Since tubulin is a highly conserved protein target critical for survival in all cell types, we expected that, as for other colchicine domain tubulin inhibitors, trends in potency and in photoswitchability of

Novel unit B cryptophycin analogues as payloads for targeted therapy

• Eduard Figueras,
• Adina Borbély,
• Mohamed Ismail,
• Marcel Frese and
• Norbert Sewald

Beilstein J. Org. Chem. 2018, 14, 1281–1286, doi:10.3762/bjoc.14.109

• glycol spacer with a terminal azide results in a complete loss of activity. Docking studies of the novel cryptophycin analogues to β-tubulin provided a rationale for the observed cytotoxicities. Keywords: cryptophycin; cytotoxic agents; novel payloads; tubulin inhibitors; tumour targeting; Introduction

Stereoselective synthesis of fused tetrahydroquinazolines through one-pot double [3 + 2] dipolar cycloadditions followed by [5 + 1] annulation

• Xiaofeng Zhang,
• Kenny Pham,
• Shuai Liu,
• Marc Legris,
• Alex Muthengi,
• Jerry P. Jasinski and
• Wei Zhang

Beilstein J. Org. Chem. 2016, 12, 2204–2210, doi:10.3762/bjoc.12.211

• , potassium channel, mPGES-1, and tubulin inhibitors, as well as the immunomodulatory drug thalidomide [28][29][30][31][32] (Figure 1). Results and Discussion Our initial effort was focused on the development of reaction conditions for the one-pot double [3 + 2] cycloadditions. The first [3 + 2] cycloaddition