Platelet aggregation inhibiting and anticoagulant effects of oligoamines, XVI: Cytostatic and cytotoxic side effects of oligoamines.
Selected synthetic oligoamines were able to inhibit (IC50) the growth of leukemic L 1210 cells in concentrations between 4-10 mumol/L. The essential structural features were at least two basic nitrogen functions in suitable distance, substituted with arylalkyl or alkyl groups. The favorable chain length is about eight carbon atoms. The cytostatic effect is complete after 30 min and cannot be washed out with buffer. Viability measurements showed that the leukemic cells were killed in a time dependent manner. As no influence on the cell nucleus could be observed this is most probably due to interaction with the cell membrane. When high local concentrations are applied in vivo, the oligoamines are toxic because of cytolytic properties. This toxicity can be overcome by administration of suitable prodrugs (LD50 greater than 1000 mg/kg).
Rehse
K
K
Institut für Pharmazie, Freien Universität Berlin.
Noack
B
B
Maurer
R
R
Hilgard
P
P
D000818:Animals; D000925:Anticoagulants / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007928:Lethal Dose 50; D007939:Leukemia L1210 / Q000188:drug therapy; D051379:Mice; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D011073:Polyamines / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D012854:Sister Chromatid Exchange / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects
D000925:Anticoagulants; D000970:Antineoplastic Agents; D010975:Platelet Aggregation Inhibitors; D011073:Polyamines