Nucleoside analogues: 8. Some isomers of B.3839, the original 5-fluorouracil/nitrosourea molecular combination, and their effect on colon, breast and lung tumours in mice.
This study describes the manipulation of secondary products arising from the synthesis of the prototypical molecular combination of 5-fluorouracil (5-FU) and chloroethylnitrosourea (CNU), B.3839, in order to investigate the effects produced by connecting the C-S-C-C-CNU chain to the 5-FU ring in different ways. The isolation of phthalimide precursors of these compounds and the transformation into CNUs is described. Anti-tumour activity of these molecular combinations against a series of experimental murine colon, lung and mammary tumours is presented. The spectrum of anti-tumour activity displayed is interesting but defies simple explanation without further detailed in vivo pharmacokinetic and metabolism studies in order to define optimal profiles for activity.
McElhinney
R S
RS
Laboratories of the Medical Research Council of Ireland, Trinity College, Dublin.
McCormick
J E
JE
Bibby
M C
MC
Double
J A
JA
Atassi
G
G
Dumont
P
P
Pratesi
G
G
Radacic
M
M
D000230:Adenocarcinoma / Q000188:drug therapy*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000627:therapeutic use*; D055598:Chemical Phenomena; D002621:Chemistry; D003110:Colonic Neoplasms / Q000188:drug therapy*; D004354:Drug Screening Assays, Antitumor; D005038:Ethylnitrosourea / Q000031:analogs & derivatives* / Q000032:analysis / Q000627:therapeutic use; D005472:Fluorouracil / Q000031:analogs & derivatives* / Q000032:analysis* / Q000138:chemical synthesis / Q000627:therapeutic use; D007536:Isomerism; D008175:Lung Neoplasms / Q000188:drug therapy*; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D009607:Nitrosourea Compounds / Q000138:chemical synthesis / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D009607:Nitrosourea Compounds; C017139:1-(2-chloroethyl)-1-nitrosourea; C060633:B 3839; D005038:Ethylnitrosourea; D005472:Fluorouracil