Nucleoside analogues: 7. Effect on colon, breast and lung tumours in mice of 5-fluorouracil/nitrosourea molecular combinations incorporating alkoxy and oxidized sulphur functions.
This study considers further changes in the carrier moiety of molecular combinations of the pyrimidine antimetabolite 5-fluorouracil (5-FU) and the alkylating group chloroethylnitrosourea (CNU). Detailed chemical syntheses are described of compounds incorporating (a) a simpler alkoxy group in the 'sugar' fragment, (b) attachment of the 5-FU residue to the C-X-C-C chain on the side of the heteroatom X distal from the CNU group, and (c) higher oxidation states of the sulphur atom in the prototypical compound B.3839. Anti-tumour activity of these analogues against a series of experimental murine colon, lung and mammary tumours is described. The pattern of activity reveals that the carrier moiety is important but further pharmacokinetics and metabolism studies are required to determine structure-activity relationships.
McElhinney
R S
RS
Laboratories of the Medical 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; D003110:Colonic Neoplasms / Q000188:drug therapy*; D004338:Drug Combinations; D004353:Drug Evaluation, Preclinical; D005472:Fluorouracil / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008175:Lung Neoplasms / Q000188:drug therapy*; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy*; D051379:Mice; D009368:Neoplasm Transplantation; D009607:Nitrosourea Compounds / Q000138:chemical synthesis* / Q000627:therapeutic use; D013329:Structure-Activity Relationship
D004338:Drug Combinations; D009607:Nitrosourea Compounds; D005472:Fluorouracil