TY - JOUR
T1 - Structure-activity relationship study of gatastatin based on the TOPLISS tree approach
AU - Hayakawa, Ichiro
AU - Shioda, Shuya
AU - Chinen, Takumi
AU - Usui, Takeo
AU - Kigoshi, Hideo
N1 - Funding Information:
This work was supported by a Grants-in-Aid for Scientific Research (C) (Grant Number JP17K01949) from the Japan Society for the Promotion of Science (JSPS). I.H. thanks the Okayama Foundation for Science and Technology for financial support.
Publisher Copyright:
© 2019 The Japan Institute of Heterocyclic Chemistry Received
PY - 2019
Y1 - 2019
N2 - - Various analogues of gatastatin, a y-tubulin-specific inhibitor, were designed and synthesized by systematically optimizing the aromatic ring at the 07-benzyl group in accordance with an operational Topliss tree, and their biological activities were evaluated. Some derivatives showed stronger cytotoxicity against HeLa cells than gatastatin. Especially, the cytotoxicity of the meta-chloro derivative was about 18-fold stronger than that of gatastatin. However, these derivatives did not exhibit binding ability to the yeast y-tubulin small complex or inhibitory activity against a,ß-tubulin polymerization. These results suggested that y-tubulin strongly recognized the unsubstituted phenyl ring of the 07-benzyl group in gatastatin.
AB - - Various analogues of gatastatin, a y-tubulin-specific inhibitor, were designed and synthesized by systematically optimizing the aromatic ring at the 07-benzyl group in accordance with an operational Topliss tree, and their biological activities were evaluated. Some derivatives showed stronger cytotoxicity against HeLa cells than gatastatin. Especially, the cytotoxicity of the meta-chloro derivative was about 18-fold stronger than that of gatastatin. However, these derivatives did not exhibit binding ability to the yeast y-tubulin small complex or inhibitory activity against a,ß-tubulin polymerization. These results suggested that y-tubulin strongly recognized the unsubstituted phenyl ring of the 07-benzyl group in gatastatin.
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U2 - 10.3987/COM-18-S(F)16
DO - 10.3987/COM-18-S(F)16
M3 - Article
AN - SCOPUS:85069524040
SN - 0385-5414
VL - 99
SP - 238
EP - 247
JO - Heterocycles
JF - Heterocycles
IS - 1
ER -