The synthesis of the studied compounds was carried out on the basis of products of three-component cyclization of S-alkylisothiuronium salts, malondinitrile (or ethylcyanoacetate) and an aromatic aldehyde under basic catalysis. The resulting 5-cyanopyrimidine derivatives were further subjected to direct oxidation under the action of oxone, or transformed into 4-amino-5- derivatives cyanopyrimidine followed by oxidation. The synthesized compounds showed high cytotoxic activity against a broad spectrum of tumor lines: A549, A431, MCF-7, HCT-116 (IC50=0.3–35 mkM). In the study of selected hit-compounds, a pronounced reducing of the migration activity of A549 lung cancer cells was established by the method of wound healing and A549 cell spheroid migration assay after 48 hours of cultivation with compounds (Fig.1 A,B). To study the mechanism of inhibition of cell migration, we performed a cell cycle analysis. According to the obtained data, the derivatives of 5-cyanopyrimidines synthesized by us cause the G2/M cell cycle arrest during cultivation with A549 cell lines in non-cytotoxic concentration (Fig.1C). Consequently, the derivatives obtained by us possess high cytotoxic activity, inhibit the migration activity of tumor cells due to arrest of the cell cycle.

Design, synthesis, and evaluation of biological properties of new 5-cyanopyrimidine-based compounds

2019 Spring National Meeting

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.