RESUMO
A series of novel 2-(5-aminomethylene-4-oxo-2-thioxothiazolidin-3-yl)-3-phenylpropionic acid ethyl esters has been synthesized. Target compounds were evaluated for their trypanocidal activity towards Trypanosoma brucei brucei and Trypanosoma brucei gambiense. Several hit-compounds (8, 10, 12) inhibited growth of the parasites at sub-micromolar concentrations (IC50 0.027-1.936⯵M) and showed significant selectivity indices (SIâ¯=â¯108-1396.2) being non-toxic towards the human primary fibroblasts. The screening of anticancer activity in vitro within NCI DTP protocol allowed to identify active 2-(5-{[5-(2,4-dichlorobenzyl)-thiazol-2-ylamino]-methylene}-4-oxo-2-thioxothiazolidin-3-yl)-3-phenylpropionic acid ethyl ester 14 that demonstrated inhibition against all 59 human tumor cell lines with the average GI50 value of 2.57⯵M. It was established that the activity type (antitrypanosomal or anticancer) as well as its level depends on the character of enamine fragment in the C5 position of thiazolidinone core.
Assuntos
Antiprotozoários/farmacologia , Tiazolidinas/farmacologia , Tripanossomicidas/farmacologia , Trypanosoma brucei brucei/efeitos dos fármacos , Animais , Antiprotozoários/síntese química , Antiprotozoários/química , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Testes de Sensibilidade Parasitária , Ratos , Relação Estrutura-Atividade , Tiazolidinas/síntese química , Tiazolidinas/química , Tripanossomicidas/síntese química , Tripanossomicidas/químicaRESUMO
5-Hydroxy-7-methyl-3H-thiazolo[4,5-b]pyridin-2-one was obtained by the reaction of 4-iminothiazolidin-2-one with acetoacetic ester. Further structural modifications include the introduction of diversity at the C5 and C6 positions. The anti-inflammatory action of novel thiazolo[4,5-b]pyridine-2-one derivatives was evaluated in vivo employing the carrageenan- induced rat paw edema method. The antioxidant activity of the synthesized compounds was evaluated in vitro by the method of scavenging effect on 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals.