1. Eur J Med Chem. 2010 Nov;45(11):5234-42. Epub 2010 Aug 21.

Studies on quinones. Part 46. Synthesis and in vitro antitumor evaluation of
aminopyrimidoisoquinolinequinones.

Vásquez D, Rodríguez JA, Theoduloz C, Calderon PB, Valderrama JA.

Facultad de Química, Pontificia Universidad Católica de Chile, Casilla 306,
Santiago 6094411, Chile.

In the search of structure-activity relationship studies and to explore the
antitumor effect associated with the pyrimidoisoquinolinequinone scaffold,
several diversily substituted 8-aminopyrimido[4,5-c]isoquinolinequinones were
regioselectively synthesized. Variation in the structure of the nitrogen
substituent bonded to the 8-position of the pyrimidoisoquinolinequinone system
led to a set of alkylamino-, phenylamino- and alkyphenylamino derivatives. The
cytotoxic activity of the aminoquinone derivatives was evaluated in vitro using
the MTT colorimetric method against one normal cell line (MRC-5 lung fibroblasts)
and four human cancer cell lines (AGS human gastric adenocarcinoma; SK-MES-1
human lung cancer cells, and J82 human bladder carcinoma; HL-60 human leukemia)
in 72-h drug exposure assays. Among the series, five compounds exhibited
interesting antitumor activity against AGS human gastric adenocarcinoma and human
lung cancer cells. The SAR studies revealed that both the nature of the nitrogen 
substituent into the quinone ring and the methyl group at the 6-position play key
roles in the antitumor activity.


PMID: 20828890 [PubMed - in process]