Synthesis and biological evaluation of new 1,5-diazaanthraquinones with cytotoxic activity.
A series of 1,5-diazaanthraquinone derivatives was synthesized and their in vitro cytotoxic activities were evaluated against several human cancer cell lines. The 1,5-diazaanthraquinone chromophore has been synthesized either on the basis of hetero Diels-Alder reactions involving different quinoline-5,8-diones and alpha,beta-unsaturated aldehyde N,N-dimethylhydrazones or by thermolysis of different arylaminomethylene Meldrum's acid derivatives. Some of these compounds showed cytotoxic activity comparable to that of mitoxantrone against most of the cell lines tested. Compounds 20, 30, 31 and 37 were 4-54 times more potent that mitoxantrone against A549, H116, PSN1 and T98G cancer cell lines but, interestingly, they were 3-16 times less potent against the human breast carcinoma SKBR3. Some structure-activity relationships are described, the most significant one being the increase in cytotoxicity resulting from the introduction of a halogen atom at the C-4 position.
Manzanaro
Sonia
S
Instituto Biomar, S.A., Polígono Industrial, Edificio CEEI, 24231 Onzonilla, León, Spain.
Vicent
María Jesús
MJ
Martín
María Jesús
MJ
Salvador-Tormo
Nélida
N
Pérez
José María
JM
del Mar Blanco
María
M
Avendaño
Carmen
C
Menéndez
José Carlos
JC
de la Fuente
Jesús Angel
JA
D000880:Anthraquinones / Q000138:chemical synthesis* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D008942:Mitoxantrone; D013329:Structure-Activity Relationship
D000880:Anthraquinones; D000970:Antineoplastic Agents; D008942:Mitoxantrone