Synthesis of carbamate derivatives of iejimalides. Retention of normal antiproliferative activity and localization of binding in cancer cells.
The syntheses of six iejimalide carbamate derivatives are described. Their biological activity and those of the unmodified iejimalides A and B against breast and prostate cancer cell lines were determined. These results show that the serine hydroxyl group of iejimalides A and B is a permissive site that can be functionalized to form carbamate derivatives without significant loss of normal biological activity. This method of derivatization will be valuable for cellular target identification, mechanism of action studies, and drug development efforts. A fluorescent derivative does not exhibit binding to the cytoskeletal features of cancer cells.
Schweitzer
Dirk
D
Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USA.
Zhu
Junyi
J
Jarori
Gotam
G
Tanaka
Junichi
J
Higa
Tatsuo
T
Davisson
V Jo
VJ
Helquist
Paul
P
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D002219:Carbamates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014561:Urochordata / Q000737:chemistry
D000970:Antineoplastic Agents; D002219:Carbamates; D018942:Macrolides; C520299:iejimalide C; C520301:iejimalide B; C520298:iejimalide D; C520300:iejimalide A