Studies with 2,5-piperazinedione, 3,6-bis(5-chloro-2-piperidyl)-,dihydrochloride. III. Biochemical and therapeutic effects in L1210 leukemias sensitive and resistant to alkylating agents: comparison with melphalan, cyclophosphamide, and BCNU.
2,5-Piperazinedione, 3,6-bis(5-chloro-2-piperidyl)-,dihydrochloride (NSC-135758) selectively inhibits DNA synthesis in L1210/0 leukemia and in cyclophosphamide-resistant L1210 (L1210/CPA). Melphalan (L-PAM) inhibits nucleic-acid synthesis but not protein synthesis in L1210/0 and L1210/CPA. CPA selectively inhibits DNA synthesis in L1210/0 but does not inhibit DNA synthesis in L1210/CPA. NSC-135758 is as active in vivo against L1210/CPA and BCNU-resistant L1210 (L1210/BCNU) as it is against L1210/0. It is inactive against ic implanted L1210/0. These data clearly indicate important differences in the biologic activity of this compound compared to either CPA or BCNU. L-PAM is similar to NSC-135758 in activity against L1210/CPA and L1210/BCNU.
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D002330:Carmustine / Q000494:pharmacology / Q000627:therapeutic use; D002478:Cells, Cultured; D003520:Cyclophosphamide / Q000494:pharmacology / Q000627:therapeutic use; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D007939:Leukemia L1210 / Q000188:drug therapy* / Q000473:pathology; D008558:Melphalan / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D010879:Piperazines / Q000627:therapeutic use*; D010880:Piperidines / Q000627:therapeutic use*
D000903:Antibiotics, Antineoplastic; D004273:DNA, Neoplasm; D010879:Piperazines; D010880:Piperidines; D003520:Cyclophosphamide; D008558:Melphalan; D002330:Carmustine