The synthesis and the study of the antitumor activity of 3-R-6-(4-methoxyphenyl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine hydrobromides

V. O. Yanchenko, Yu. A. Fedchenkova, A. M. Demchenko


Aim. To synthesize and study the antitumor activity of 3-R-6-(4-methoxyphenyl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine derivatives.

Results and discussion. To determine the antitumor activity of 3-R-6-(4-methoxyphenyl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine hydrobromides, the in vitro study was conducted 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) according to the standard procedure of the mitotic activity assessment of new potential bioactive compounds by the fluorescent coloring method (sulforhodamine B as a dye). It was performed in the US National Сancer Institute within the Development Therapeutic Program. It has been found that derivatives of 3-R-6-(4-methoxyphenyl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine exhibit the antineoplastic activity against a wide range of cancer cells lines and are promising core structures for creating new effective anticancer agents.

Experimental part. 3-R-6-(4-methoxyphenyl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine hydrobromides were synthesized by the interaction of 4-amino-5-R-4H-1,2,4-triazole-3-thiols with 4-methoxyphenacyl bromide in ethyl acetate. The 1Н NMR spectra were recorded on a Bruker VXR-300 spectrometer (Germany) with the working frequency of 299.945 MHz.

Conclusions. A series of 3-R-6-(4-methoxyphenyl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine hydrobromides has been synthesized. The anticancer activity of the compounds obtained has been studied in the National Cancer Institute on 60 lines of tumor cells. Compounds that exhibit high levels of the antitumor activity have been found. It has been shown that the replacement of 3-H in compound 3a with ethyl or pentyl radicals leads to increase in the antitumor activity against MDA-MB-468 breast cancer cells.

Received: 04.02.2020
Revised: 03.09.2020
Accepted: 17.09.2020


7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine; anastrozole; antitumor activity

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Abbreviated key title: J. Org. Pharm. Chem.

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