title: 20-O-acylcamptothecin derivatives: evidence for lactone stabilization.
abstract: Convincing UV and NMR spectrophotometric evidence is presented which demonstrates that at physiological pH, 7.4, 20-O-acyl derivatives of camptothecin (CPT) are substantially more stable in the lactone form than the 20-OH parent. Additionally, it was determined by HPLC analysis that the lactone ring of a 20-O-ether derivative of CPT underwent endocyclic ring opening at pH > or =8.5, while the lactone ring of 20-O-acyl CPT derivatives remained unaffected. PEG (and other smaller alkyl) 20-O-acyl-CPT derivatives released native CPT at pH > 9.5, which arises from exocyclic cleavage, thus precluding isolation of any open CPT acyl PEG (or alkyl) carboxylate forms.
authors.affiliation: Enzon, Inc., Piscataway, New Jersey 08854-3969, USA.
authors.forename: H
authors.initials: H
authors.lastname: Zhao
authors.forename: C
authors.initials: C
authors.lastname: Lee
authors.forename: P
authors.initials: P
authors.lastname: Sai
authors.forename: Y H
authors.initials: YH
authors.lastname: Choe
authors.forename: M
authors.initials: M
authors.lastname: Boro
authors.forename: A
authors.initials: A
authors.lastname: Pendri
authors.forename: S
authors.initials: S
authors.lastname: Guan
authors.forename: R B
authors.initials: RB
authors.lastname: Greenwald
mesh_terms: D000215:Acylation; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000378:metabolism; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D007783:Lactones / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism; D011355:Prodrugs / Q000737:chemistry / Q000378:metabolism; D013056:Spectrophotometry, Ultraviolet; D014197:Trees / Q000737:chemistry
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D007783:Lactones; D011355:Prodrugs; D011092:Polyethylene Glycols; C115093:pegamotecan; D002166:Camptothecin