title: A thalidomide analogue with in vitro antiproliferative, antimitotic, and microtubule-stabilizing activities.
abstract: 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.
authors.affiliation: 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
authors.forename: Pui-Kai
authors.initials: PK
authors.lastname: Li
authors.forename: Bulbul
authors.initials: B
authors.lastname: Pandit
authors.forename: Dan L
authors.initials: DL
authors.lastname: Sackett
authors.forename: Zhigen
authors.initials: Z
authors.lastname: Hu
authors.forename: Jennifer
authors.initials: J
authors.lastname: Zink
authors.forename: Jiandong
authors.initials: J
authors.lastname: Zhi
authors.forename: Dena
authors.initials: D
authors.lastname: Freeman
authors.forename: Robert W
authors.initials: RW
authors.lastname: Robey
authors.forename: Karl
authors.initials: K
authors.lastname: Werbovetz
authors.forename: Andrew
authors.initials: A
authors.lastname: Lewis
authors.forename: Chenglong
authors.initials: C
authors.lastname: Li
mesh_terms: 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*
chemical_list: 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