Synthesis, DNA interaction and antineoplastic activity of semicarbazone derivatives.
A number of antineoplastic agents including procarbazine and bisantrene derive from hydrazine, but so far none have been developed from semicarbazide. In order to assay active minimal structures, thirteen new compounds were prepared by replacing hydrogen atoms in semicarbazone amine group by alkylamine moieties, employing an improved procedure. DNA binding was evaluated by treatment of a drug solution with DNA-cellulose complex and further measurement of remaining drug by UV spectroscopy and the affinity observed to range from medium to weak. On testing these compounds against human neoplastic cell lines, only a nitroderivative proved active on CNS and Breast cell lines at 10(-4) M. This member was studied by cyclic voltammetry.
Asís
S E
SE
Departamento de Química Orgánica, Facultad de Farmacia y Bioquímica UBA, Buenos Aires, Argentina.
Bruno
A M
AM
Molina
D A
DA
Conti
G M
GM
Gaozza
C H
CH
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004247:DNA / Q000737:chemistry / Q000187:drug effects*; D004563:Electrochemistry; D006801:Humans; D012664:Semicarbazones / Q000138:chemical synthesis* / Q000494:pharmacology; D013056:Spectrophotometry, Ultraviolet; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D012664:Semicarbazones; D004247:DNA