Synthesis of thiazole linked chalcones and their pyrimidine analogues as anticancer agents

Abstract

A series of nine novel thiazole linked chalcones, (E)-3-(4-methyl-2-(4(trifluoromethyl)phenyl)thiazol-5-yl)-1-phenylprop-2-en-1-one derivatives 7–15 were synthesized. To establish the structure–activity relationship (SAR), furthermore, the corresponding, ring-closed pyrimidine analogs 17–23 were synthesized. The derivatives thus obtained were evaluated for their anti-cancer activity against three genetically different colorectal cancer (CRC) cell lines. Thiazole derivatives 7, 9, and10 showed anti-cancer activity with GI50 values ranging from 0.19 to 100 µM. Importantly, compounds 7 and 10 outperformed the standard drug cisplatin in the tested cell lines and thus show promise for further optimization. Some of pyrimidine derivatives retain activity comparable to cisplatin in the HT-29 cell line, e.g. compounds 17 and 18 with IC50 of 25 µM, however, none of these compounds demonstrated improved antiproliferative activity as compared with the starting thiazole, thus the enone linker was critical for obtaining more active compounds in this series.

Graphical Abstract

Keywords:

• Anticancer activity
• chalcone derivatives
• medicinal chemistry
• pyrimidines
• thiazoles

Acknowledgments

The authors are thankful to Faculty of Health and Medical Sciences, University of Copenhagen.

Disclosure statement

No potential conflict of interest was reported by the author(s).