Rationale for the synthesis and preliminary biological evaluation of highly active new antitumor nitrosoureido sugars.
Various new nitrosoureido derivatives of di- or trideoxy sugars were synthesized. The influence of the hydroxyl substitution pattern, the configuration at the anomeric center, and the absolute configuration of the sugar moiety on the antitumor activity of a series of nitrosoureido derivatives of di- and trideoxy sugars was studied. All compounds showed a very significant activity in vivo against L1210 leukemia, B16 melanocarcinoma, and Lewis lung carcinoma. Methyl 3-[3-(2-chloroethyl)-3-nitrosoureido]-2,3-dideoxy-alpha-D-arabino- hexopyranoside, 24 (NSC 609224), was found to be the most active compound. When treated with 24 (NSC 609224) at 20 mg/kg on day 1, at least 90% of the L1210 leukemia and B16 melanocarcinoma bearing mice showed a survival of over 60 days for a LD50 value for this compound of 42 mg/kg.
Roger
P
P
Département de Chimie Thérapeutique, Institut Choay, Montrouge, France.
Monneret
C
C
Fournier
J P
JP
Choay
P
P
Gagnet
R
R
Gosse
C
C
Letourneux
Y
Y
Atassi
G
G
Gouyette
A
A
D000606:Amino Sugars / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000633:toxicity; D055598:Chemical Phenomena; D002621:Chemistry; D004353:Drug Evaluation, Preclinical; D007928:Lethal Dose 50; D007939:Leukemia L1210 / Q000188:drug therapy; D008546:Melanoma, Experimental / Q000188:drug therapy; D051379:Mice; D008811:Mice, Inbred DBA; D009374:Neoplasms, Experimental / Q000188:drug therapy; D009607:Nitrosourea Compounds / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D013329:Structure-Activity Relationship
D000606:Amino Sugars; D000970:Antineoplastic Agents; D009607:Nitrosourea Compounds