Anti-Parasite and Cytotoxic Activities of Chloro and Bromo L-Tyrosine Derivatives

Abstract

A series of twenty-one L-tyrosine derivatives with modifications in the halogenation pattern of the aromatic ring and different degree of methylations on the amine and phenolic hydroxyl groups were synthesized. The structures of all the intermediates and target compounds were confirmed unambiguous by spectroscopy analysis. Additionally, all compounds were evaluated against Plasmodium falciparum and Leishmania panamensis parasites between 20-702 µg mL -1 . The cytotoxic evaluation was done to determine the selectivity index for each compound. Six compounds had the lower EC 50 (effective concentration 50) against L. panamensis. One of these compounds was the most active with an EC 50 at 24.13 µg mL -1 (76.07 µM). All derivatives showed no significant activity against P. falciparum and no compound has in vitro antifungal activity at 500 µg mL -1 .

Antimicrobial Chlorinated 3-Phenylpropanoic Acid Derivatives from the Red Sea Marine Actinomycete Streptomyces coelicolor LY001

“…Finally, HMBC of H-2/C-3 (qC, δ C 120.8), H-2/C-4 (qC, δ C 151.7), H-5/C-4, H-5/C-3, H-5/C-1 (qC, δ C 133.5), H 2 -7/C-9 (qC, δ C 173.9), and H 2 -8/C-9 ( Figure 3) supported the substitution on the benzene ring in 3. Again, the chemical shifts of the 1 H (H-2, H-5 and H-6) and 13 C (C-1-C-6) NMR signals of the 3,5-dichloro-4-hydroxy phenyl moiety in compound 3 are similar with reported data for (S)-3-(3-chloro-4-hydroxyphenyl)-2-(dimethylamino)propanoic acid [42]. Thus, 3 was assigned as 3-(3-chloro-4-hydroxyphenyl)propanoic acid and this is the first report about its natural occurrence.…”

“…Further, the assignment of the substituents on the aromatic moiety was supported by HMBC ( Figure 3) as previously discussed under compound 1. Similarly, the 1 H chemical shifts of H-2 and H-6, and 13 C chemical shifts values of C-1-C-6 in 2 are similar to those of (S)-2-amino-3-(3,5-dichloro-4-hydroxyphenyl)-propanoic acid [42]. Accordingly, compound 2 was assigned as 3-(3,5-dichloro-4-hydroxyphenyl)propanoic acid methyl ester and this is its first natural occurrence.…”

“…Thus, 3,5-dichloro-4-hydroxyphenyl moiety was assigned as part A of the molecule ( Figure 2 ). Furthermore, the 1 H chemical shifts values of H-2 and H-6, and 13 C values of C-1–C-6 in 1 are similar with those of ( S )-2-amino-3-(3,5-dichloro-4-hydroxyphenyl)-propanoic acid [ 42 ]. The substituent at C-1 of the phenyl moiety was assigned as 3-substituted propanoic acid (part B) as supported from the signals at δ H/C 2.86 (2H)/29.3 (H 2 -7/C-7), 2.64 (2H)/34.5 (H 2 -8/C-8), and δ C 173.8 (qC, C-9) ( Table 1 ).…”