title: Efficient and chemoselective N-acylation of 10-amino-7-ethyl camptothecin with poly(ethylene glycol).
abstract: A new poly(ethylene glycol) (PEG) conjugate of 10-amino-7-ethyl camptothecin, a potent antitumor analogue of camptothecin, has been synthesized and preliminary in vivo tests have been performed. Successful chemoselective N-acylation of 10-amino-7-ethyl camptothecin was accomplished using phenyl dichlorophosphate, a coupling reagent used in esterification of alcohols, while other coupling methods failed, due to the low nucleophilicity of the amino group in position 10. The conjugate was tested against P388 murine leukemia cell lines and resulted equipotent to CPT-11, a camptothecin analogue already in clinical use.
authors.affiliation: Department of Pharmaceutical Sciences, University of Padova - via F Marzolo, 5 35131 Padova, Italy. andrea.guiotto@unipd.it
authors.forename: Andrea
authors.initials: A
authors.lastname: Guiotto
authors.forename: Mirta
authors.initials: M
authors.lastname: Canevari
authors.forename: Piero
authors.initials: P
authors.lastname: Orsolini
authors.forename: Olivier
authors.initials: O
authors.lastname: Lavanchy
authors.forename: Christine
authors.initials: C
authors.lastname: Deuschel
authors.forename: Norimasa
authors.initials: N
authors.lastname: Kaneda
authors.forename: Akinobu
authors.initials: A
authors.lastname: Kurita
authors.forename: Takeshi
authors.initials: T
authors.lastname: Matsuzaki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yaegashi
authors.forename: Seigo
authors.initials: S
authors.lastname: Sawada
authors.forename: Francesco M
authors.initials: FM
authors.lastname: Veronese
mesh_terms: D000215:Acylation; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000378:metabolism*; D013237:Stereoisomerism
chemical_list: D011092:Polyethylene Glycols; D002166:Camptothecin