Synthesis and in Vitro Cytotoxic Evaluation of Aminoquinones Structurally Related to Marine Isoquinolinequinones

Molecules

Virginia Delgado¹  Andrea Ibacache¹  Cristina Theoduloz¹ 

[1] ¹Facultad de Química, Pontificia Universidad Católica de Chile, Casilla 306, Santiago 6094411, Chile ²Facultad de Ciencias de la Salud, Universidad de Talca, Talca 3460000, Chile ³Instituto de Etno-Farmacología (IDE), Universidad Arturo Prat, Casilla 121, Iquique 1100000, Chile

关键词: aminoisoquinoline-5;    8-quinones;    regioselectivity;    anticancer;    SAR analysis;   

DOI  :  10.3390/molecules17067042

来源: mdpi

【 摘 要 】

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 mM range, lower than the anti-cancer agent etoposide used as reference.

【 授权许可】

CC BY   
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.