3-(5-AMINO-4-CYANOOXAZOL-2-YL)COUMARINS DERIVATIVES: SYNTHESIS AND BIOLOGICAL PROPERTIES
DOI: https://doi.org/10.17721/1728-2209.2023.1(58).12
Keywords:
2-amino-3,3-dichloroacrylonitrile, (2-imino)coumarin, 5-amino-4-cyanoxazole, heterocyclization, effect on cancer cell growth.Abstract
Background. The practical use of 3-hetarylcoumarin derivatives relates to their valuable spectral and biological characteristics, which are determined by the nature of the substituents in the basic structure. Earlier, on the base of 2-amino-3,3-dichloroacrylonitrile (ADAN), the method for the synthesis of new oxazole derivatives was developed by us, and the possibility of 5-amino-4-cyanooxazol-2-yl)acetate's obtaining by its following cyclization into the coumarin cycle was shown. In this study, the synthesis of new 3-(5-amino-4-cyanoxazol-2-yl)coumarins, as well as determination of their ability to inhibit the growth of cancer cells, were represented.
The objects of investigation are heterocyclization as a method for 3-(5-amino-4-cyanoxazol-2-yl)coumarins obtaining, as well as spectral and biological characteristics of the synthesized substances.
Methods. Organic synthesis of new derivatives of (5-amino-4-cyanoxazol-2-yl)acetic acid and 3-(5-amino-4-cyanoxazol-2-yl)coumarin; characterization of the synthesized substances using 1Н, 13С NMR spectroscopy and chromatography-mass spectrometry; single-dose tests of anticancer activity of three derivatives on 60 cancer cell lines.
Results. Based on ADAN, a number of new derivatives of 3-(5-amino-4-cyanoxazol-2-yl)coumarin were synthesized in different ways: 1) formation of (5-amino-4-cyanoxazol-2-yl)acetic acid derivatives and their subsequent cyclization with salicylic aldehydes into coumarins; 2) acylation of the ADAN amino group with coumarin-3-carboxylic acid chloroanhydride and subsequent formation of an oxazole substituent at the 3-position of coumarin under the action of amines. It has been established that the anticancer activity of 3-(5-amino-4-cyanoxazol-2-yl)coumarins is generally very low, and they are able to slightly slow down the growth of only certain lines.
Conclusions. It is shown that for the synthesis of 3-(5-amino-4-cyanoxazol-2-yl)coumarins derivatives (in particular, compounds with active functional groups – hydroxyl, ester) two alternative synthetic schemes can be successfully applied, and due to the convenience of the techniques, it is possible to easily achieve a large variety of such derivatives. The low anticancer activity of some synthesized derivatives is consistent with the low toxicity inherent in the majority of 3-hetarylcoumarins.
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