Antitumor effect and toxicity of two new active-site-directed irreversible ornithine decarboxylase and extrahepatic arginase inhibitors.
The irreversible ornithine decarboxylase and extrahepatic arginase inhibitors (+)-S-2-amino-5-iodoacetamidopentanoic acid (2-AIPA) and (+)-S-2-amino-6-iodoacetamidohexanoic acid (2-AIHA) were evaluated. The LD50 tests were made in rats and mice using both compounds. Rats and mice were treated with either 2-AIPA or 2-AIHA i.p. for a period of 180 days. The treated animals showed a decrease of total serum proteins and increased ALT and AST levels. CK was also modified but inversely related to dose. Protection tests were carried out using L5178Y mouse lymphosarcoma. The mean survival time for each treated group was calculated and the percentage T/C was determined. For 2-AIPA it was 170 and for 2-AIHA it was 210 at 15 mg/kg.
Trujillo-Ferrara
J
J
Sección de Graduados, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico, D.F.
Koizumi
G
G
Muñoz
O
O
Joseph-Nathan
P
P
Yañez
R
R
D000596:Amino Acids / Q000494:pharmacology* / Q000633:toxicity; D000614:Aminocaproates; D015119:Aminocaproic Acid / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000633:toxicity; D001119:Arginase / Q000037:antagonists & inhibitors*; D004354:Drug Screening Assays, Antitumor; D007940:Leukemia L5178 / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D065108:Ornithine Decarboxylase Inhibitors; D051381:Rats; D017208:Rats, Wistar
D000596:Amino Acids; D000614:Aminocaproates; D000970:Antineoplastic Agents; D065108:Ornithine Decarboxylase Inhibitors; C079267:2-amino-5-iodoacetamidopentanoic acid; C079268:2-amino-6-iodoacetamidohexanoic acid; D001119:Arginase; D015119:Aminocaproic Acid