| Autor: |
Krasnov VP; Postovsky Institute of Organic Synthesis, Russian Academy of Sciences (Ural Branch), 620108 Ekaterinburg, Russia., Vozdvizhenskaya OA; Postovsky Institute of Organic Synthesis, Russian Academy of Sciences (Ural Branch), 620108 Ekaterinburg, Russia., Baryshnikova MA; Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, 115522 Moscow, Russia., Pershina AG; Center of Bioscience and Bioengineering, Siberian State Medical University, 634050 Tomsk, Russia.; Research School of Chemical and Biomedical Engineering, National Research Tomsk Polytechnic University, 634050 Tomsk, Russia., Musiyak VV; Postovsky Institute of Organic Synthesis, Russian Academy of Sciences (Ural Branch), 620108 Ekaterinburg, Russia., Matveeva TV; Postovsky Institute of Organic Synthesis, Russian Academy of Sciences (Ural Branch), 620108 Ekaterinburg, Russia., Nevskaya KV; Center of Bioscience and Bioengineering, Siberian State Medical University, 634050 Tomsk, Russia., Brikunova OY; Center of Bioscience and Bioengineering, Siberian State Medical University, 634050 Tomsk, Russia., Gruzdev DA; Postovsky Institute of Organic Synthesis, Russian Academy of Sciences (Ural Branch), 620108 Ekaterinburg, Russia., Levit GL; Postovsky Institute of Organic Synthesis, Russian Academy of Sciences (Ural Branch), 620108 Ekaterinburg, Russia. |
| Abstrakt: |
Testing a number of N -[omega-(purin-6-yl)aminoalkanoyl] derivatives of 7,8-difluoro-3,4-dihydro-3-methyl-2 H -[1,4]benzoxazine in a panel of nine tumor cell lines has shown that the studied compounds exhibit high cytotoxic activity, especially against 4T1 murine mammary carcinoma, COLO201 human colorectal adenocarcinoma, SNU-1 human gastric carcinoma, and HepG2 human hepatocellular carcinoma cells. Synthesis and study of structural analogs of these compounds made it possible to find that the presence of both a difluorobenzoxazine fragment and a purine residue bound via a linker of a certain length is crucial for the manifestation of the cytotoxic activity of this group of compounds. The study of the effect of the most promising compound on the cell cycle of the human tumor cell lines, the most sensitive and least sensitive to cytotoxic action (MDA-MB-231 breast adenocarcinoma and COLO201 colorectal adenocarcinoma, respectively), allows us to conclude that this compound is an inhibitor of DNA biosynthesis. The found group of purine conjugates may be of interest in the design of new antitumor agents. |
