Synthesis and trypanocide activity of chloro-l-tyrosine and bromo-l-tyrosine derivatives

• DOI: 10.1007/s00044-018-2249-y
• Publication Date: 2018-09-25T08:31:24Z
• Authors: Manuel Pastrana R...; Elkin Galeano Jar...; Alejandro Martíne...; Sara Robledo Rest...
• Keywords: 0303 health sciences; 03 medical and health sciences; 3. Good health

Twenty-two halogenated l-tyrosine derivatives were synthesized to examine new substances for the treatment of Chagas disease. The synthesis of these derivatives with different degree of substitution in the amino group with methyl iodide, giving primary, tertiary, and quaternary amino acids. All compounds were tested in vitro against intracellular amastigotes of Trypanosoma cruzi, and the cytotoxicity were evaluated over monocytic cell line U-937. Compound 25 was the most active against T. cruzi with a EC50 of 75.52 µM compared with benznidazole with a EC50 of 58.79 µM. Compounds 3, 4, 7, and 15 were the derivatives with the best selectivity index (SI) with values of 7.5, 8.3,12.1, and 8.6, respectively. Finally, compound 7 was the safer and the more promising derivative against T. cruzi.