synthesis and in vitro cytotoxic evaluation of aminoquinones structurally related to marine isoquinolinequinones合成和体外细胞毒性评价海洋isoquinolinequinones aminoquinones结构有关.pdfVIP

Molecules 2012, 17, 7042-7056; doi:10.3390/molecule OPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Article Synthesis and in Vitro Cytotoxic Evaluation of Aminoquinones Structurally Related to Marine Isoquinolinequinones Virginia Delgado 1, Andrea Ibacache 1, Cristina Theoduloz 2 and Jaime A. Valderrama 1,3,* 1 Facultad de Química, Pontificia Universidad Católica de Chile, Casilla 306, Santiago 6094411, Chile 2 Facultad de Ciencias de la Salud, Universidad de Talca, Talca 3460000, Chile 3 Instituto de Etno-Farmacología (IDE), Universidad Arturo Prat, Casilla 121, Iquique 1100000, Chile * Author to whom correspondence should be addressed; E-Mail: jvalderr@uc.cl; Tel.: +56-02-686-4432; Fax: +56-02-686-4744. Received: 18 April 2012; in revised form: 23 May 2012 / Accepted: 25 May 2012 / Published: 7 June 2012 Abstract: 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