title: Synthesis and cytotoxic evaluation of some carbohydrazones and thiocarbohydrazones of various unsaturated ketones and related Mannich bases.
abstract: A number of 1-aryl-1-penten-3-ones 1 and related Mannich bases 2 were synthesized and converted either directly or indirectly to the corresponding biscarbohydrazones 3 and 4. Reaction of representative unsaturated ketones with thiocarbohydrazide led to the formation of only the monothiocarbohydrazones 5. The cytotoxicity of these compounds against murine P388 and L1210 cells, human T-lymphocytes and human tumour cell lines was undertaken in order to ascertain their bioactivity and review these data in the light of the theory of sequently cytotoxicity whereby the carbohydrazones would be predicted to be more than twice as cytotoxic as the ketones and Mannich bases from which they were derived. In general, conversion of 1 into 3 was accompanied by a lowering of cytotoxicity. On the other hand, in general the compounds in series 4 were significantly more potent cytotoxic agents than the analogues 2; in fact, some compounds displayed activity comparable with or exceeding that of melphalan. Thus the biscarbohydrazones 4 represent a novel group of cytotoxic agents serving as lead molecules for subsequent development.
authors.affiliation: College of Pharmacy and Nutrition, University of Saskatchewan, Canada.
authors.forename: J R
authors.initials: JR
authors.lastname: Dimmock
authors.forename: P
authors.initials: P
authors.lastname: Kumar
authors.forename: T M
authors.initials: TM
authors.lastname: Allen
authors.forename: G Y
authors.initials: GY
authors.lastname: Kao
authors.forename: S
authors.initials: S
authors.lastname: Halleran
authors.forename: J
authors.initials: J
authors.lastname: Balzarini
authors.forename: E
authors.initials: E
authors.lastname: de Clercq
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D006835:Hydrazones / Q000138:chemical synthesis* / Q000494:pharmacology; D066298:In Vitro Techniques; D007939:Leukemia L1210 / Q000188:drug therapy; D007941:Leukemia P388 / Q000188:drug therapy; D051379:Mice; D013601:T-Lymphocytes / Q000187:drug effects; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D006835:Hydrazones