Diarylsemicarbazones: synthesis, antineoplastic activity and topoisomerase I inhibition assay.
A series of diarylsemicarbazones was synthesized and tested against human neoplastic cell lines. The more active members have a l-naphthyl ring at the carbamidic nitrogen, and chloro, dimethylamino or nitro group substituents at the benzylidene moiety. None of these showed affinity to DNA. One of the more active compounds was tested as a topoisomerase I inhibitor and showed a potent effect. SAR studies demonstrated linear correlation between lypophilicity and activity on the most sensitive lines and a definite conformational shape for antineoplastic action.
Asís
S E
SE
Departamento de Química Orgánica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
Bruno
A M
AM
Martínez
A R
AR
Sevilla
M V
MV
Gaozza
C H
CH
Romano
A M
AM
Coussio
J D
JD
Ciccia
G
G
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001391:Azo Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D004563:Electrochemistry; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D001391:Azo Compounds; D004791:Enzyme Inhibitors; D059004:Topoisomerase I Inhibitors; D004247:DNA