RESUMEN
Herein we describe the synthesis of 1,2,4-triazolyl-3-thione;1,3,4-oxadiazole, and imidazo[2,1-b]thiazole derivatives from carbohydrates. The antiviral activity of these compounds was tested against Dengue and Junin virus (the etiological agent of Argentine hemorrhagic fever). The 3-(p-bromobenzoyl)-5-(1,2-O-isopropylidene-3-O-methyl-alpha-d-xylofuranos-5-ulos-5-yl)imidazo[2,1-b]thiazole was able to inhibit the replication of both viruses in Vero cells at concentration significantly lower than the CC(50).
Asunto(s)
Antivirales/síntesis química , Antivirales/farmacología , Azoles/síntesis química , Azoles/farmacología , Carbohidratos/química , Virus del Dengue/efectos de los fármacos , Virus Junin/efectos de los fármacos , Animales , Antivirales/toxicidad , Azoles/química , Azoles/toxicidad , Chlorocebus aethiops , Concentración 50 Inhibidora , Pruebas de Toxicidad , Células Vero/efectos de los fármacosRESUMEN
Two series of imidazo[2,1-b]thiazoles substituted on C-3 or C-5 with an unprotected carbohydrate moiety were synthesized. Different protective groups for position 3 of the carbohydrate moiety were tested (acetyl, tert-butyldimethylsilyl (TBDMS), and p-methoxybenzyl (PMB)) and the latter turn out to be the best strategy to obtain the desired products. Full deprotection of the carbohydrate was performed successfully in only one step.
Asunto(s)
Carbohidratos/química , Imidazoles/síntesis química , Tiazoles/síntesis química , Imidazoles/química , Estructura Molecular , Estereoisomerismo , Tiazoles/químicaRESUMEN
Herein, we describe the syntheses of 3,5-disubstituted imidazo[2,1-b]thiazole. The cyclization step was performed in two different conditions by using either thermal or microwave heating. Comparing the results of both methodologies, we found that the microwave assistance is an improved alternative to obtain this family of heterocyclic compound. Compounds were first evaluated for cytotoxicity in Vero cells by MTT method and then, the antiviral activity was assayed by a virus yield inhibition assay in the range of concentrations lower than the corresponding CC(50), using JUNV strain IV4454 as the model system. The most active compounds (3 and 4), showed a level of antiviral activity against JUNV in monkey Vero cells better than the reference substance ribavirin. Then, they are promising lead compound for further analysis and characterization to establish their therapeutic potential against hemorrhagic fever viruses.