In Vitro Activity of Heterocyclic Compounds with a Pyrazole Ring and a Diterpene Isolated from Marine Algae Against Herpes Simplex Virus Type 1
1e4Miranda, M.D.; 2Bueno, L.B.; 3Azevedo, R.A.; 2Pereira, R.C.; 2Teixeira, V.L.; 3Bernardino, A.M.L.; 4Mignaco J.A.; 1Frugulhetti, I.C.P.P.; 4Fontes C.F.L.
1Departamento de Biologia Celular e Molecular, 2Departamento de Biologia Marinha, 3Departamento de Química Orgânica, 4Instituto de Bioquímica Médica.
1,2,3Universidade Federal Fluminense e 4Universidade Federal do Rio de Janeiro – RJ – Brasil
The discovery of new classes of compounds with potent antiviral activity is important not only for the development of potential therapeutic agents against various viral diseases, but also for the study of mechanisms of antiviral effects. Infection by Herpes Simplex virus type-1 is one of the most important pandemics. Many compounds used to treat HSV-1 associated pathologies, like Acyclovir (ACV), can be neurotoxic; in addition, many ACV-resistant strains of HSV-1 have been described. Thus, the seek for new compounds with less citotoxicity and more selectivity is extremely important. Vero cells were infected with an ACV-resistant strain of HSV-1 and titers were measured in the presence or absence of 20μM of Dolabellan (a compound from Dictyota sp. algae), and of 50μM of the diterpene Benzonaftiridine. These molecules could inhibit the HSV-1 cytophatic effect up to 90%. We evaluated their cytotoxicity by Trypan blue dye exclusion. Dolabellan showed a CC50 above 90μM while Benzonaftiridine compounds showed a CC50 greater than 700 μM. We could select the compounds AM-15, AM-57, AM-63, ARA-04 and ARA-05 from the pyrazole system. These molecules showed less citotoxicity toward Vero cells, as a resut they presented a very low selectivity index. To characterize at which step of the HSV-1 replicative cycle these compounds acted, we performed a time-course of infection, and observed that compounds ARA-04 and ARA-05 inhibited HSV-1 adsorption on Vero cells. Therefore, these compounds could be used as basis for the development of new antiviral drugs.
|