title: N2,N4,N6-tri(hydroxymethyl)-N2,N4,N6-trimethylmelamine (trimelamol) is an efficient DNA cross-linking agent in vitro.
abstract: An investigation of the mechanism of action of the antitumour agent trimelamol has established that it is an efficient interstrand DNA cross-linker in vitro, comparable to nitrogen mustards such as melphalan. Studies have shown that the cross-linking reaction is acid-catalysed but, unlike the nitrogen mustards, only partially reversible after treatment with piperidine. The bisalkylation (cross-linking) reaction appears to be concerted, and no "second arm" reaction has been detected. The results of thermal denaturation studies are consistent with general DNA binding, and suggest a preference for GC-rich sites. The acid-catalysed reaction of trimelamol with a model nucleophile (thiophenol) has also been investigated and an adduct resulting from displacement of the three carbinolamine functions has been isolated and characterized.
authors.affiliation: School of Pharmacy and Biomedical Sciences, Portsmouth Polytechnic, Hants.
authors.forename: C
authors.initials: C
authors.lastname: Jackson
authors.forename: J A
authors.initials: JA
authors.lastname: Hartley
authors.forename: T C
authors.initials: TC
authors.lastname: Jenkins
authors.forename: R
authors.initials: R
authors.lastname: Godfrey
authors.forename: R
authors.initials: R
authors.lastname: Saunders
authors.forename: D E
authors.initials: DE
authors.lastname: Thurston
mesh_terms: D000970:Antineoplastic Agents / Q000378:metabolism* / Q000494:pharmacology; D003432:Cross-Linking Reagents / Q000378:metabolism; D004247:DNA / Q000187:drug effects / Q000378:metabolism*; D004277:DNA, Single-Stranded / Q000187:drug effects / Q000378:metabolism; D004587:Electrophoresis, Agar Gel; D007700:Kinetics; D013696:Temperature; D014227:Triazines / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D003432:Cross-Linking Reagents; D004277:DNA, Single-Stranded; D014227:Triazines; C049507:trimelamol; D004247:DNA