Searching Anti-Zika Virus Activity in 1H-1,2,3-Triazole Based Compounds

Molecules

Ronaldo N. de Oliveira¹  Willyenne M. Dantas¹  Diogo A. L. Santos²  Gustavo Seabra²  Lindomar J. Pena³  Valentina N. M. de Oliveira⁴  Prem P. Sharma⁵  Brijesh Rathi⁵ 

[1] Department of Chemistry, Federal Rural University of Pernambuco, Recife 52171-900, Brazil;Department of Fundamental Chemistry, Federal University of Pernambuco, Recife 50740-540, Brazil;Department of Virology, Aggeu Magalhães Institute (IAM), Oswaldo Cruz Foundation (Fiocruz), Recife 50670-420, Brazil;Instituto Federal de Educação Ciência e Tecnologia de Pernambuco, Campus Ipojuca, Ipojuca 55590-000, Brazil;Laboratory for Translational Chemistry and Drug Discovery, Department of Chemistry, Hansraj College, University of Delhi, Delhi 110007, India;

关键词: Zika virus;    cytotoxicity;    1H-1,2,3-triazoles;    phthalimide;    naphthoquinone;    MD simulation;   

DOI  :  10.3390/molecules26195869

来源: DOAJ

【 摘 要 】

Zika virus (ZIKV) is a mosquito-borne virus belonging to the Flaviviridae family and is responsible for an exanthematous disease and severe neurological manifestations, such as microcephaly and Guillain-Barré syndrome. ZIKV has a single strand positive-sense RNA genome that is translated into structural and non-structural (NS) proteins. Although it has become endemic in most parts of the tropical world, Zika still does not have a specific treatment. Thus, in this work we evaluate the cytotoxicity and antiviral activities of 14 hybrid compounds formed by 1H-1,2,3-triazole, naphthoquinone and phthalimide groups. Most compounds showed low cytotoxicity to epithelial cells, specially the 3b compound. After screening with all compounds, 4b was the most active against ZIKV in the post-infection test, obtaining a 50% inhibition concentration (IC₅₀) of 146.0 µM and SI of 2.3. There were no significant results for the pre-treatment test. According to the molecular docking compound, 4b was suggested with significant binding affinity for the NS5 RdRp protein target, which was further corroborated by molecular dynamic simulation studies.

【 授权许可】

Unknown