title: Structure-activity relationship studies of thalidomide analogs with a taxol-like mode of action.
abstract: Anti-microtubule agents such as paclitaxel and docetaxel have played an important role in the treatment of cancer for many years. Recently, a small molecule that has a taxol-like mode of action (5HPP-33) was reported. Herein, the detailed structure-activity relationship (SAR) studies of 5HPP-33 analogs that are substituted at the isoindole and phenyl rings are described. Bulky substitutions (such as di-isopropyl groups) on the phenyl ring result in the isoindole and phenyl rings being perpendicular to each other. It was found that this conformation is critical for anti-microtubule activity. These studies have provided valuable information, which will be helpful in the design of more potent analogs.
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, United States.
authors.forename: Bulbul
authors.initials: B
authors.lastname: Pandit
authors.forename: Zhigen
authors.initials: Z
authors.lastname: Hu
authors.forename: Somsundaram N
authors.initials: SN
authors.lastname: Chettiar
authors.forename: Jennifer
authors.initials: J
authors.lastname: Zink
authors.forename: Zili
authors.initials: Z
authors.lastname: Xiao
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Etter
authors.forename: Deepak
authors.initials: D
authors.lastname: Bhasin
authors.forename: Pui-Kai
authors.initials: PK
authors.lastname: Li
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D054833:Isoindoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008870:Microtubules / Q000737:chemistry* / Q000378:metabolism; D017239:Paclitaxel / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D050257:Tubulin Modulators / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: C501339:2-(2,6-diisopropylphenyl)-5-hydroxy-1H-isoindole-1,3-dione; D054833:Isoindoles; D050257:Tubulin Modulators; D013792:Thalidomide; D017239:Paclitaxel
keywords: Anti-microtubule agents; Thalidomide analogs