In vitro Anti-HMPV Activity of New Synthetic Phenytoin Derivatives

Journal of the Brazilian Chemical Society

Mendes, Gabriella¹  Romanos, Maria T. V.¹  Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil¹  Universidade de Brasília, Brasília, Brazil¹  Arruda, Ana L. A.¹  Aspesi, Geisa H.¹  Andrade, Carlos K. Z.¹  Universidade Católica Dom Bosco, Campo Grande, Brazil¹ 

关键词:  phenytoin;    1;    2;    3-triazoles;    metapneumovirus;    antiviral assay;    real-time RT-PCR;   

DOI  :  10.5935/0103-5053.20150234

学科分类：化学（综合）

来源: SciELO

【 摘 要 】

New derivatives of synthetic 5,5-diphenylhydantoin (phenytoin) were prepared by N-alkylation with 1,3-dibromopropane. Subsequent treatment with sodium azide led to the respective azide. Reaction of the azide with phenylacetylene and 2-hydroxy-3-butyne and oxidation of the resulting alcohol with MnO2 resulted in three triazolic compounds that were evaluated in vitro for their antiviral activity against human metapneumovirus (HMPV). 5,5-Diphenyl-3-[3-(4-phenyl-1H-1,2,3-triazol-1-yl)propyl]imidazolidine-2,4-dione was the most active of the three compounds tested, with selectivity index of 129.87, even higher than ribavirin, the control substance. The three compounds showed activity in the early stages of viral replication presenting virucidal activity and binding to cellular receptors, preventing the adsorption of viral particles. These compounds showed higher activity in both experiments, inhibiting 98.3% of infection as virucidal and 98.9% when interacting with cellular receptors. Furthermore, they showed 73.8% of activity during the penetration of HMPV particles into cells. The derivative 3-{3-[4-(1-hydroxyethyl)-1H-1,2,3-triazol-1-yl]propyl}-5,5-diphenylimidazolidine-2,4-dione presented a mild anti-HMPV activity, with selectivity index of 2.74. 3-[3-(4-acetyl-1H-1,2,3-triazol-1-yl)propyl]-5,5-diphenylimidazolidine-2,4-dione inhibited less than 50% of HMPV replication.

【 授权许可】

Unknown