Synthesis and cytotoxicity evaluation of thiazole conjugated amino acid derivatives

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, whic...

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Main Authors: Nhut Linh Huynh, Truong Giang Nguyen, Thi My Tien Nguyen, Pham Xuan Truc Nguyen, Minh Thi Bui, Trong Hieu Le, Vinh Quang Hong, Minh Kiep Do, Hiroyuki Morita, Thi Buu Hue Bui
Format: Article
Language:English
Published: Can Tho University Publisher 2025-06-01
Series:CTU Journal of Innovation and Sustainable Development
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Online Access:https://ctujs.ctu.edu.vn/index.php/ctujs/article/view/1054
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Summary: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).
ISSN:2588-1418
2815-6412