title: Synthesis and evaluation of 1,2,2-tris(sulfonyl)hydrazines as antineoplastic and trypanocidal agents.
abstract: Several 1,2,2-tris(sulfonyl)hydrazines, conceived as prodrugs of 1,2-bis(sulfonyl)hydrazines, were synthesized and evaluated for antineoplastic and trypanocidal activities in mice. 1-Methyl-1,2,2-tris(methylsulfonyl)hydrazine emerged as an extremely efficacious antitrypanosomal agent, whereas 1-(2-chloroethyl)-1,2,2-tris(methylsulfonyl)hydrazine was inactive. In contrast, 1-(2-chloroethyl)-1,2,2-tris(methylsulfonyl)hydrazine displayed potent antineoplastic activity, producing several 60-day "cures" of mice bearing leukemia L1210, leukemia P388, or Sarcoma 180. Furthermore, the fact that the tris(sulfonyl) derivatives will not generate isocyanates, which contribute to the host toxicity of nitrosoureas like 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), makes them agents of significant promise in trypanosomal and cancer chemotherapy.
authors.affiliation: Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06510.
authors.forename: K
authors.initials: K
authors.lastname: Shyam
authors.forename: P G
authors.initials: PG
authors.lastname: Penketh
authors.forename: A A
authors.initials: AA
authors.lastname: Divo
authors.forename: R H
authors.initials: RH
authors.lastname: Loomis
authors.forename: C L
authors.initials: CL
authors.lastname: Patton
authors.forename: A C
authors.initials: AC
authors.lastname: Sartorelli
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use; D055598:Chemical Phenomena; D002621:Chemistry; D005260:Female; D006834:Hydrazines / Q000138:chemical synthesis* / Q000627:therapeutic use; D007939:Leukemia L1210 / Q000188:drug therapy; D007941:Leukemia P388 / Q000188:drug therapy; D051379:Mice; D015394:Molecular Structure; D011355:Prodrugs / Q000138:chemical synthesis / Q000627:therapeutic use; D012510:Sarcoma 180 / Q000188:drug therapy; D013450:Sulfones / Q000138:chemical synthesis* / Q000627:therapeutic use; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000627:therapeutic use; D014346:Trypanosoma brucei brucei; D014353:Trypanosomiasis, African / Q000188:drug therapy; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D006834:Hydrazines; D011355:Prodrugs; D013450:Sulfones; D014344:Trypanocidal Agents