A thalidomide analogue with in vitro antiproliferative, antimitotic, and microtubule-stabilizing activities.
We discovered a thalidomide analogue [5-hydroxy-(2,6-diisopropylphenyl)-1H-isoindole-1,3-dione (5HPP-33)] with antiproliferative activity against nine cancer cell lines in vitro. Flow cytometric analyses showed that the compound caused G2-M arrest, which occurred mainly at the mitotic phase. In addition, immunofluorescence microscopy and in vitro tubulin polymerization studies showed that 5HPP-33 has antimicrotubule activity with a paclitaxel-like mode of action. It is effective against four different paclitaxel-resistant cell lines. Thus, 5HPP-33 represents a potential antitumor agent.
Li
Pui-Kai
PK
Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, 338 Parks Hall, 500 West 12th Avenue, Columbus, OH 43210-1291, USA. li.27@osu.edu
Pandit
Bulbul
B
Sackett
Dan L
DL
Hu
Zhigen
Z
Zink
Jennifer
J
Zhi
Jiandong
J
Freeman
Dena
D
Robey
Robert W
RW
Werbovetz
Karl
K
Lewis
Andrew
A
Li
Chenglong
C
D000818:Animals; D050256:Antimitotic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D054833:Isoindoles; D051379:Mice; D017239:Paclitaxel / Q000494:pharmacology; D014404:Tubulin / Q000187:drug effects; D050257:Tubulin Modulators / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
C501339:2-(2,6-diisopropylphenyl)-5-hydroxy-1H-isoindole-1,3-dione; D050256:Antimitotic Agents; D000970:Antineoplastic Agents; D007211:Indoles; D054833:Isoindoles; D014404:Tubulin; D050257:Tubulin Modulators; D017239:Paclitaxel