Studies on quinones. Part 41: synthesis and cytotoxicity of isoquinoline-containing polycyclic quinones.
In the search for new potentially anticancer drugs, isoquinolinequinone-containing polycyclic compounds have been designed and synthesized through highly regiocontrolled cycloaddition reactions of methyl 1,3-dimethyl-5,8-dioxo-5,8-dihydroisoquinoline-4-carboxylate with polarized 1,3-dienes and a thiazole-o-quinodimethane. The new N-heterocyclic quinones were tested on normal human fibroblasts and four distinct human cancer cell lines. Two of the evaluated compounds displayed significant in vitro activity (IC50: 0.44-5.9 microM) comparable to that of the reference drug etoposide.
Facultad de Química, Pontificia Universidad Católica de Chile, Casilla 306, Santiago, Chile. jvalderr@uc.cl
Jaime A
JA
Valderrama
M Florencia
MF
González
David
D
Pessoa-Mahana
Ricardo A
RA
Tapia
Houda
H
Fillion
Felix
F
Pautet
Jaime A
JA
Rodriguez
Cristina
C
Theoduloz
Guillermo
G
Schmeda-Hirschmann
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D045744:Cell Line, Tumor; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D005047:Etoposide / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D011809:Quinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D000970:Antineoplastic Agents; D011809:Quinones; D005047:Etoposide