Synthesis and virucide activity on zika virus of 1,2,3-triazole-containing vanillin derivatives

The Zika virus (ZIKV) is an arbovirus and belongs to the Flaviviridae family and Flavivirus genus, with dissemination in the Americas. In Brazil, the predominant strain is the Asian, promoting outbreaks that started in 2015 and are directly related to microcephaly in newborns and Guillain-Barré synd...

Full description

Saved in:

Bibliographic Details
Published in:	Antiviral research Vol. 212; p. 105578
Main Authors:	da Silva Rodrigues, João Vitor, Rodrigues Gazolla, Poliana Aparecida, da Cruz Pereira, Iago, Dias, Roberto Sousa, Poly da Silva, Italo Esposti, Oliveira Prates, John Willians, de Souza Gomes, Isabela, de Azevedo Silveira, Sabrina, Costa, Adilson Vidal, de Oliveira, Fabrício Marques, de Aguiar, Alex Ramos, Canedo da Silva, Cynthia, Teixeira, Róbson Ricardo, de Paula, Sérgio Oliveira
Format:	Journal Article
Language:	English
Published:	Netherlands Elsevier B.V 01-04-2023
Subjects:	Adult Animals Antiviral molecules Chlorocebus aethiops Humans Infant, Newborn Molecular Docking Simulation Triazole core Vanillin Vero Cells Virus Replication Zika fever Zika Virus Zika Virus Infection - prevention & control Antiviral molecules Vanillin Zika fever Triazole core
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	The Zika virus (ZIKV) is an arbovirus and belongs to the Flaviviridae family and Flavivirus genus, with dissemination in the Americas. In Brazil, the predominant strain is the Asian, promoting outbreaks that started in 2015 and are directly related to microcephaly in newborns and Guillain-Barré syndrome in adults. Recently, researchers identified a new African strain circulating in Brazil at the mid-end of 2018 and the beginning of 2019, with the potential to originate a new epidemic. To date, there is no approved vaccine or drug for the treatment of Zika syndrome, and the development of therapeutic alternatives to treat it is of relevance. A critical approach is to use natural products when searching for new chemical agents to treat Zika syndrome. The present investigation describes the preparation of a series of 1,2,3-triazoles derived from the natural product vanillin and the evaluation of their virucide activity. A series of fourteen derivatives were prepared via alkylation of vanillin followed by CuAAC (the copper(I)-catalyzed azide-alkyne cycloaddition) reaction. The compounds were fully characterized by infrared (I.R.), nuclear magnetic resonance (NMR), and high-resolution mass spectrometry (HRMS) techniques. The cytotoxicity of Vero cells and the effect on the Zika Virus of the vanillin derivatives were evaluated. It was found that the most effective compound corresponded to 4-((1-(4-isopropylbenzyl)-1H-1,2,3-triazol-4-yl)methoxy)-3-methoxybenzaldehyde (8) (EC50 = 27.14 μM, IC50 = 334.9 μM). Subsequent assessments, namely pre and post-treatment assays, internalization and adsorption inhibition assays, kinetic, electronic microscopy analyses, and zeta potential determination, revealed that compound 8 blocks the Zika virus infection in vitro by acting on the viral particle. A molecular docking study was performed, and the results are also discussed. •There is no approved vaccine for the Zika syndrome.•Development of therapeutic alternatives to treat it is of relevance.•We describe the preparation of a series of 1,2,3-triazoles derived.•Compound 8 blocks the Zika virus infection in vitro by acting on the viral particle.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0166-3542 1872-9096
DOI:	10.1016/j.antiviral.2023.105578