On 9-amino derivatives of ellipticine and a comparative study on DNA apurinic site cleavage and mutagenicity
Lefrançois, M.; Lescot, E.; Psaume, B.; Malvy, C.; Virlizier, H.; Boissart, C.; Gauduchon, P.
Farmaco 47(9): 1197-1206
1992
ISSN/ISBN: 0014-827X PMID: 1300125 Document Number: 402397
The synthesis of 9-aminoellipticine (IV) has been improved by amination of 9-bromoellipticine according to the Goldberg reaction. Also via the Goldberg procedure we obtained 9-methylamino-ellipticine (VI) with the aim to reduce the mutagenicity of (IV). Eventhough 2-methyl-9-aminoellipticinium acetate (VII) has been mentioned in a previous paper, no details were given for its preparation. We therefore synthesized this compound in such a way as to obtain a monoquaternary salt where only the pyridinic nitrogen bears the positive charge. The study of cleavage induced by 10 mu-M of (IV) and (VII) on a plasmid DNA (PM2) containing a low concentration of apurinic sites shows that (VII) possesses the same property of cleavage at apurinic sites as (IV) and reaches almost complete cleavage despite its slower reaction rate. The quaternized derivative (VII) is not mutagenic on tested Salmonella strains in contrast with its free base (IV).