Synthesis and cytotoxicity evaluation of thiazole conjugated amino acid derivatives

Abstract

This paper presents the three-step synthesis and cytotoxicity evaluation of the thiazole-conjugated amino acid derivatives. Starting from the commercially available benzophenone and thiourea, the thiazole structure was successfully constructed bearing the free amino groups at the C-2 position, which was then coupled with the carboxyl functionality of N-Boc L-phenylalanine, N-Boc L-proline and N-Boc L-tryptophane using CDI as the coupling reagent under mild basic conditions to provide the hybrid thiazole/N-Boc amino acid derivatives 5a-c. Finally, the acidic promoted deprotection of the Boc groups afforded the desired hybrid thiazole/amino acid derivatives 6a-c in reasonable total yields. Cytotoxicity assays indicated that the hybrids thiazole/L-proline (6a) and thiazole/L-tryptophan (6c) exhibited rather good cytotoxicity on the cervical cancer cell line (IC50 =18.86 and 18.25 µM, respectively). Notably, compound 5a having the thiazole conjugated with unprotected N-Boc L-phenylalanine showed very good activity towards the lung cancer (IC50 = 15.72 µM), the cervical cancer (IC50 = 8.98 µM) and the breast cancer cell lines (IC50 = 8.07 µM), which were 1.3-, 1.2-and 2.5-fold, respectively, stronger activity than 5-FU (IC50 = 20.73, 10.67 and 20.43 µM, respectively).