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 .
Despite the serious public health problem represented by the diseases caused by dengue (DENV), Zika (ZIKV) and chikungunya (CHIKV) viruses, there are still no specific licensed antivirals available for their treatment. Here, we examined the potential anti-arbovirus activity of ten di-halogenated compounds derived from L-tyrosine with modifications in amine and carboxyl groups. The activity of compounds on VERO cell line infection and the possible mechanism of action of the most promising compounds were evaluated. Finally, molecular docking between the compounds and viral and cellular proteins was evaluated in silico with Autodock Vina®, and the molecular dynamic with Gromacs®. Only two compounds (TDC-2M-ME and TDB-2M-ME) inhibited both ZIKV and CHIKV. Within the possible mechanism, in CHIKV, the two compounds decreased the number of genome copies and in the pre-treatment strategy the infectious viral particles. In the ZIKV model, only TDB-2M-ME inhibited the viral protein and demonstrate a virucidal effect. Moreover, in the U937 cell line infected with CHIKV, both compounds inhibited the viral protein and TDB-2M-ME inhibited the viral genome too. Finally, the in silico results showed a favorable binding energy between the compounds and the helicases of both viral models, the NSP3 of CHIKV and cellular proteins DDC and β2 adrenoreceptor.
Novel iodotyramides with para-substituted benzoic acids were synthesized via electrophilic aromatic substitutions and amide coupling via N,N'-diisopropylcarbodiimide (DIC) in dimethylformamide (DMF). All derivatives were in vitro screened against U-937 macrophages and Plasmodium falciparum, Leishmania panamensis and Trypanosoma cruzi protozoan parasites. The hemolytic activity was evaluated on human red blood cells (RBC). -methoxyphenethyl)-4-methoxybenzamide were the most active against L. panamensis with an effective concentration 50 (EC 50 ) of 17.9 and 17.5 μg mL -1 , respectively; while compounds N- (3,5-diiodo-4-methoxyphenethyl)-4-methylbenzamide and N-(3,5-diiodo-4-methoxyphenethyl
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