A chemical platform for the efficient screening of arylazopyrazole-based photoswitchable CENP-E inhibitors using mild cyclization reactions

Kazuya Matsuo; Honoka Ogawa; Shusuke Yamaoka; Tomonori Waku; Akio Kobori

doi:10.1016/j.bmcl.2024.129892

A chemical platform for the efficient screening of arylazopyrazole-based photoswitchable CENP-E inhibitors using mild cyclization reactions

Bioorg Med Chem Lett. 2024 Oct 1:111:129892. doi: 10.1016/j.bmcl.2024.129892. Epub 2024 Jul 17.

Authors

Kazuya Matsuo¹, Honoka Ogawa², Shusuke Yamaoka², Tomonori Waku², Akio Kobori²

Affiliations

¹ Faculty of Molecular Chemistry and Engineering, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan. Electronic address: kmatsuo@kit.ac.jp.
² Faculty of Molecular Chemistry and Engineering, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan.

PMID: 39029538
DOI: 10.1016/j.bmcl.2024.129892

Abstract

A set of arylazopyrazole-based inhibitors targeting the mitotic motor protein CENP-E was discovered through the chemical platform using the quantitative cyclization of 1,3-diketone intermediate with various hydrazines under mild conditions. Through this efficient platform, the structure-activity relationship pertaining to the pyrazole photoswitch in photoswitchable CENP-E inhibitors not only in vitro but also in cells was successfully clarified.

Keywords: Arylazopyrazole; CENP-E; Photopharmacology; Photoswitch.

MeSH terms

Azo Compounds / chemical synthesis
Azo Compounds / chemistry
Azo Compounds / pharmacology
Chromosomal Proteins, Non-Histone* / antagonists & inhibitors
Chromosomal Proteins, Non-Histone* / metabolism
Cyclization
Dose-Response Relationship, Drug
Humans
Molecular Structure
Pyrazoles* / chemical synthesis
Pyrazoles* / chemistry
Pyrazoles* / pharmacology
Structure-Activity Relationship

Substances

Pyrazoles
Chromosomal Proteins, Non-Histone
centromere protein E
Azo Compounds
pyrazole