Design, synthesis of new pyrimidine derivatives as anticancer and antimicrobial agents

A new series of 6-aryl-5-cyano thiouracil derivatives were synthesized. Cyanouracil <b>1</b> was condensed with monochloroacetic acid and different aldehydes to give thiazolopyrimidine <b>2</b>. On the other hand, treatment of cyanouracil <b>1</b> with 2-chloro-<i>N</i>-substituted-phenylac etamide afforded <b>4</b>. Hydrazinolysis of <b>6</b> afforded the hydrazino derivatives <b>7</b> which upon reaction with different electrophilic reagents such as acetic anhydride, benzoyl chloride, and carbon disulfide yielded pyrimidine derivatives <b>8</b>–<b>15</b>. Some of the new derivatives were explored for their antimicrobial activities. Compounds <b>7</b> and <b>9</b> have a promising activity, relatively equipotent to the reference drug. All of the new synthesized compounds were tested <i>in vitro</i> for their antiproliferative activities against HePG-2 and MCF-7 cell lines. Compounds <b>7</b>, <b>9</b>, and <b>2d</b> displayed potent growth inhibitory effect toward the two cell lines more than the standard drug 5-FU. Furthermore, a docking study of the most active compounds was performed with thymidylate synthase enzyme.