6-bis-(2-chloroethyl)amino-6-deoxy-D-galactopyranose hydrochloride: synthesis, chemical characterization, murine P388 antitumor activity, and bone marrow toxicity.
6-Bis-(2-chloroethyl)amino-6-deoxy-D-galactopyranose hydrochloride has been synthesized, characterized, and evaluated for antitumor activity and bone marrow toxicity in mice. The 1D- and 2D-NMR studies show the compound to exist as a beta-anomer chair conformation (23%), alpha-anomer chair conformation (22%), and several equilibrating boat conformations or furanose forms (55%). A single ip LD10 dose of 15.0 mg/kg produced antitumor activity against the murine P388 leukemia superior to that achieved with an equitoxic dose of nitrogen mustard. In normal mice, this 15.0-mg/kg dose produced minimal depression of peripheral white blood cells and no significant decrease in absolute neutrophil counts. A reduction in toxicity was also demonstrated for human bone marrow CFU-GM, as compared with nitrogen mustard and L-PAM. This and other sugar-containing mustard compounds may represent a class of antineoplastic alkylating agents with reduced bone marrow toxicity.
Schein
P S
PS
Vincent T. Lombardi Cancer Research Center, Georgetown University School of Medicine, Washington, DC 20007.
Green
D
D
Hammer
C F
CF
McPherson
E
E
Talebian
A
A
D000477:Alkylating Agents; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D001853:Bone Marrow / Q000187:drug effects*; D005688:Galactosamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology / Q000633:toxicity; D006801:Humans; D007941:Leukemia P388 / Q000188:drug therapy*; D007942:Leukemia, Experimental / Q000188:drug therapy*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA
D000477:Alkylating Agents; D000970:Antineoplastic Agents; C050475:C6-galactose mustard; D005688:Galactosamine