The synthesis and the study of the antitumor activity of 1,4-diaryl-5,6,7,8-tetrahydro-2,2a,8a triazacyclopenta[cd]azulene derivatives
Keywords:1, 4-diaryl-5, 6, 7, 8-tetrahydro-2, 2a, 8a-triazacyclopenta[cd]azulenes, antitumor activity
Aim. To synthesize, prove the structural framework and study the antitumor activity of 1,4-diaryl-5,6,7,8-tetrahydro-2,2a,8a-triazacyclopenta [cd]azulene derivatives.
Results and discussion. To determine the antineoplastic activity of 1-phenyl-4-aryl-5,6,7,8-tetrahydro-2,2a,8a-triazacyclopenta[cd]azulenes 7a-g and 1-(41-bromophenyl)-4-aryl-5,6,7,8-tetra-hydro-2,2a,8a-triazacyclopenta [cd]azulenes 7h-k the study in vitro was carried out on 60 lines of cancer cells (leukemia, non-small cell lung cancer, colon cancer, CNS cancer, melanoma, ovarian cancer, renal cancer, prostate cancer and breast cancer) under the effect of the substance in the concentration of 10-5 mol/l according to the standard procedure of the mitotic activity assessment of the new potential bioactive compounds by the fluorescent coloring method (sulphorhodamine B as a dye) performed in the US National Institute of cancer within the Development Therapeutic Program.
Experimental part. 2-Methoxy-3,4,5,6-tetrahydro-7H-azepine was obtained by alkylation of caprolactam with dimethyl sulfate. 3-Phenyl or (41-bromophenyl)-(6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepine 4 a,b was obtained by condensation of 2-methoxy-3,4,5,6-tetrahydro-7H-azepine 1 with 4-bromobenzoic acid hydrazide and subsequent cyclization of the intermediate product. The 1Н-NMR spectra were recorded on a Bruker VXR-300 spectrometer (Germany) with the working frequency of 299.945 MHz, in DMSO-d6 using tetramethylsilane (TMS) as an internal standard. The purity of the compounds synthesized was controlled by TLC on the Silufol UV-254 plates in the system of chloroform – methanol (9 : 1).
Conclusions. New chemical compounds – derivatives of 1-phenyl(41-bromphenyl)-4-aryl-5,6,7,8-tetrahydro-2,2a,8a-triaza-cyclopenta[cd]azulene have been synthesized. The anticancer activity of the compounds obtained on 60 lines of tumor cells in the US National Cancer Institute has been studied. The high-active compounds that exhibit high levels of the antitumor activity have been identified.
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