Bis(hetero)aryl derivatives as unique kinesin spindle protein inhibitors

Kenji Matsuno; Jun-ichi Sawada; Mina Sugimoto; Naohisa Ogo; Akira Asai

doi:10.1016/j.bmcl.2009.01.018

Bis(hetero)aryl derivatives as unique kinesin spindle protein inhibitors

Bioorg Med Chem Lett. 2009 Feb 15;19(4):1058-61. doi: 10.1016/j.bmcl.2009.01.018. Epub 2009 Jan 11.

Authors

Kenji Matsuno¹, Jun-ichi Sawada, Mina Sugimoto, Naohisa Ogo, Akira Asai

Affiliation

¹ Center for Drug Discovery, Graduate School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.

PMID: 19167222
DOI: 10.1016/j.bmcl.2009.01.018

Abstract

Synthesis of 4-(4-tert-butylphenyl)pyridine analogues as kinesin spindle protein (KSP) inhibitors, SAR, cytotoxicity and mitotic arrest in HeLa cells are described. Interestingly, PVZB1194 showed potent KSP inhibition only in the presence of microtubules and distinct KSP localization from a known KSP inhibitor S-trytylcysteine analogue in mitosis. The observations would have resulted from a different molecular mechanism of KSP inhibition and suggest a novel biological regulation for KSP in mitosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Combinatorial Chemistry Techniques
HeLa Cells
Humans
Kinesins / antagonists & inhibitors*
Kinesins / metabolism
Mitosis / drug effects*
Molecular Structure
Pyridines / chemical synthesis*
Pyridines / chemistry
Pyridines / pharmacology*
Spindle Apparatus / drug effects*
Structure-Activity Relationship

Substances

Pyridines
Kinesins