Bis(hetero)aryl derivatives as unique kinesin spindle protein inhibitors.
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.
Matsuno
Kenji
K
Center for Drug Discovery, Graduate School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
Sawada
Jun-ichi
J
Sugimoto
Mina
M
Ogo
Naohisa
N
Asai
Akira
A
D020650:Combinatorial Chemistry Techniques; D006367:HeLa Cells; D006801:Humans; D016547:Kinesins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects*; D015394:Molecular Structure; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008941:Spindle Apparatus / Q000187:drug effects*; D013329:Structure-Activity Relationship
D011725:Pyridines; D016547:Kinesins