STUDIES WITH 2,5-PIPERAZINEDIONE, 3,6-BIS(5-CHLORO-2-PIPERIDYL)-, DIHYDROCHLORIDE .3. 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, from Streptomyces griseoluteus) 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 [bis chloronitrosourea]-resistant L1210 (L1210/BCNU) as it is against L1210/0. It is inactive against intracutaneously implanted L1210/0. These data clearly indicate important differences in the biological 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.