title: Preliminary study of mechanism of action of SN38 derivatives. Physicochemical data, evidence of interaction and alkylation of DNA octamer d(GCGATCGC)2.
abstract: The synthesis of water-soluble SN38 derivatives is presented, and their stability in solutions used during drug development studies has been investigated. A preliminary study of mechanism of action of 9-aminomethyl SN38 is presented. Using NMR techniques, the interaction of the oligomer d(GCGATCGC)2is studied, showing that the terminal GC base pairs are the main site of interaction. Using pulsed field gradient spin echo and mass spectroscopy, evidence of a spontaneous alkylation reaction of the DNA oligomer with SN38 derivatives is presented. A proposed mechanism of reaction is suggested. Copyright © 2016 John Wiley & Sons, Ltd.
authors: Institute of Organic Chemistry, Polish Academy of Sciences, Warsaw, Poland.
authors: Beata
authors: B
authors: Naumczuk
authors: University of Natural Sciences and Humanities, Siedlce, Poland.
authors: Robert
authors: R
authors: Kawęcki
authors: Institute of Organic Chemistry, Polish Academy of Sciences, Warsaw, Poland.|National Medicines Institute, Warsaw, Poland.
authors: Wojciech
authors: W
authors: Bocian
authors: National Medicines Institute, Warsaw, Poland.
authors: Elżbieta
authors: E
authors: Bednarek
authors: Institute of Organic Chemistry, Polish Academy of Sciences, Warsaw, Poland.|National Medicines Institute, Warsaw, Poland.
authors: Jerzy
authors: J
authors: Sitkowski
authors: Institute of Organic Chemistry, Polish Academy of Sciences, Warsaw, Poland.|National Medicines Institute, Warsaw, Poland.
authors: Lech
authors: L
authors: Kozerski
mesh_terms: D000478:Alkylation; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry*; D001483:Base Sequence; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D004247:DNA / Q000737:chemistry*; D004355:Drug Stability; D000077146:Irinotecan; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015394:Molecular Structure; D011089:Polydeoxyribonucleotides / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D011089:Polydeoxyribonucleotides; D000077146:Irinotecan; D004247:DNA; D002166:Camptothecin
keywords: DNA; MALDI MS; NMR; SN38 derivative; covalent binding