Monoarylhydrazones of alpha-lapachone: synthesis, chemical properties and antineoplastic activity.
The biological activities of the naphthoquinones lapachol, extracted from trees of the genus Tabebuia and its cyclization products alpha and beta-lapachone, have been intensively studied. Giving continuity to the research about new derivatives obtained from the reaction of these naphthoquinones with amino-containing reagents, a series of arylhydrazones of alpha-lapachone was synthesized and their antineoplastic activity was evaluated. This new structure is based on the great electrophilicity of 1,4-quinoidal carbonyl groups towards reagents containing nitrogen as nucleophilic centers, such as arylhydrazines. The products were assayed by the National Cancer Institute (NCI, USA) and their binding to DNA, redox properties and QSAR studies were also determined.
Renou
S G
SG
Centro de Síntesis y Estudio de Nuevos Compuestos Antineoplásicos, Departamento de Química Orgánica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires (UBA), Buenos Aires, Argentina. sgrenou@ffyb.uba.ar
Asís
S E
SE
Abasolo
M I
MI
Bekerman
D G
DG
Bruno
A M
AM
D000465:Algorithms; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004247:DNA / Q000737:chemistry; D004354:Drug Screening Assays, Antitumor; D004563:Electrochemistry; D006801:Humans; D006835:Hydrazones / Q000138:chemical synthesis* / Q000494:pharmacology*; D008958:Models, Molecular; D009285:Naphthoquinones / Q000138:chemical synthesis* / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship
D000970:Antineoplastic Agents; D006835:Hydrazones; D009285:Naphthoquinones; D004247:DNA; C415043:alpha-lapachone