Synthesis and in vitro cytotoxic evaluation of aminoquinones structurally related to marine isoquinolinequinones.
The synthesis of 4-methoxycarbonyl-3-methylisoquinolinequinone (1) and a variety of its substitution products with amino-, alkylamino and halogen groups on the quinone nucleus is reported. The series of 6-, 7- and 6,7-subtituted isoquinolinequinones were evaluated in vitro for their cytotoxic activity using the MTT colorimetric method. All the newly synthesized compounds showed moderate to high potency against MRC-5 healthy lung fibroblasts and four human tumor cell lines: AGS gastric adenocarcinoma, SK-MES-1 lung, J82 bladder carcinoma, and HL-60 leukemia cells. Among the series, compounds 4b, 12 and 13 exhibited interesting antitumor activity against human gastric adenocarcinoma, human lung and human bladder carcinoma cancer cells. 7-Amino-6-bromoisoquinoline-5,8-quinone (13) was found to be the most promising active compound against the tested cancer cell lines, with IC₅₀ values in the 0.21-0.49 μM range, lower than the anti-cancer agent etoposide used as reference.
Facultad de Química, Pontificia Universidad Católica de Chile, Casilla 306, Santiago 6094411, Chile.
Virginia
V
Delgado
Andrea
A
Ibacache
Cristina
C
Theoduloz
Jaime A
JA
Valderrama
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity*; D002460:Cell Line; D002478:Cells, Cultured; D018922:HL-60 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity*; D011809:Quinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity*
D000970:Antineoplastic Agents; D007546:Isoquinolines; D011809:Quinones