{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:54:42Z","timestamp":1791928482781,"version":"4.3.4"},"reference-count":43,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2021,9,28]],"date-time":"2021-09-28T00:00:00Z","timestamp":1632787200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006162","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Ci\u00eancia e Tecnologia do Estado de Pernambuco","doi-asserted-by":"publisher","award":["APQ-0560-2.12\/19"],"award-info":[{"award-number":["APQ-0560-2.12\/19"]}],"id":[{"id":"10.13039\/501100006162","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["PQ 301308\/2017-9"],"award-info":[{"award-number":["PQ 301308\/2017-9"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["PQ 310956\/2019-6"],"award-info":[{"award-number":["PQ 310956\/2019-6"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["finance code 001"],"award-info":[{"award-number":["finance code 001"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>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-Barr\u00e9 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 \u00b5M 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.<\/jats:p>","DOI":"10.3390\/molecules26195869","type":"journal-article","created":{"date-parts":[[2021,9,28]],"date-time":"2021-09-28T21:38:09Z","timestamp":1632865089000},"page":"5869","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Searching Anti-Zika Virus Activity in 1H-1,2,3-Triazole Based Compounds"],"prefix":"10.3390","volume":"26","author":[{"given":"Willyenne M.","family":"Dantas","sequence":"first","affiliation":[{"name":"Department of Chemistry, Federal Rural University of Pernambuco, Recife 52171-900, Brazil"},{"name":"Department of Virology, Aggeu Magalh\u00e3es Institute (IAM), Oswaldo Cruz Foundation (Fiocruz), Recife 50670-420, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina N. M.","family":"de Oliveira","sequence":"additional","affiliation":[{"name":"Instituto Federal de Educa\u00e7\u00e3o Ci\u00eancia e Tecnologia de Pernambuco, Campus Ipojuca, Ipojuca 55590-000, Brazil"},{"name":"Department of Fundamental Chemistry, Federal University of Pernambuco, Recife 50740-540, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diogo A. L.","family":"Santos","sequence":"additional","affiliation":[{"name":"Department of Fundamental Chemistry, Federal University of Pernambuco, Recife 50740-540, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo","family":"Seabra","sequence":"additional","affiliation":[{"name":"Department of Fundamental Chemistry, Federal University of Pernambuco, Recife 50740-540, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prem P.","family":"Sharma","sequence":"additional","affiliation":[{"name":"Laboratory for Translational Chemistry and Drug Discovery, Department of Chemistry, Hansraj College, University of Delhi, Delhi 110007, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2133-8847","authenticated-orcid":false,"given":"Brijesh","family":"Rathi","sequence":"additional","affiliation":[{"name":"Laboratory for Translational Chemistry and Drug Discovery, Department of Chemistry, Hansraj College, University of Delhi, Delhi 110007, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindomar J.","family":"Pena","sequence":"additional","affiliation":[{"name":"Department of Virology, Aggeu Magalh\u00e3es Institute (IAM), Oswaldo Cruz Foundation (Fiocruz), Recife 50670-420, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6111-2351","authenticated-orcid":false,"given":"Ronaldo N.","family":"de Oliveira","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Federal Rural University of Pernambuco, Recife 52171-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e69","DOI":"10.1038\/emi.2017.59","article-title":"Zika virus replication in the mosquito Culex quinquefasciatus in Brazil","volume":"6","author":"Guedes","year":"2017","journal-title":"Emerg. Microbes Infect."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1021\/acsinfecdis.9b00047","article-title":"Systematic Analysis of Structure Similarity between Zika Virus and Other Flaviviruses","volume":"5","author":"Hu","year":"2019","journal-title":"ACS Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/0035-9203(52)90042-4","article-title":"Zika Virus (I). Isolations and serological specificity","volume":"46","author":"Dick","year":"1952","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2536","DOI":"10.1056\/NEJMoa0805715","article-title":"Zika Virus Outbreak on Yap Island, Federated States of Micronesia","volume":"360","author":"Duffy","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_5","first-page":"1085","article-title":"Zika virus, French Polynesia, South Pacific, 2013","volume":"20","author":"Roche","year":"2014","journal-title":"Emerg. Infect. Dis."},{"key":"ref_6","first-page":"6941735","article-title":"Revisiting key entry routes of human epidemic arboviruses into the mainland americas through large-scale phylogenomics","volume":"2018","author":"Campos","year":"2018","journal-title":"Int. J. Genom."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Lowe, R., Barcellos, C., Brasil, P., Cruz, O.G., Hon\u00f3rio, N.A., Kuper, H., and Carvalho, M.S. (2018). The zika virus epidemic in brazil: From discovery to future implications. Int. J. Environ. Res. Public Health, 15.","DOI":"10.3390\/ijerph15010096"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1016\/S1474-4422(20)30232-5","article-title":"Neurological disease in adults with Zika and chikungunya virus infection in Northeast Brazil: A prospective observational study","volume":"19","author":"Ferreira","year":"2020","journal-title":"Lancet Neurol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.ijid.2019.08.033","article-title":"Fatal Zika virus infection in the Americas: A systematic review","volume":"88","author":"Collins","year":"2019","journal-title":"Int. J. Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1981","DOI":"10.1056\/NEJMsr1604338","article-title":"Zika Virus and Birth Defects-Reviewing the Evidence for Causality","volume":"374","author":"Rasmussen","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.ejmech.2016.09.023","article-title":"Structure-activity relationship (SAR) study and design strategies of nitrogen-containing heterocyclic moieties for their anticancer activities","volume":"125","author":"Akhtar","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.ebiom.2017.09.034","article-title":"Chloroquine, a FDA-approved Drug, Prevents Zika Virus Infection and its Associated Congenital Microcephaly in Mice","volume":"24","author":"Li","year":"2017","journal-title":"EBioMedicine"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.antiviral.2016.11.023","article-title":"The FDA-approved drug sofosbuvir inhibits Zika virus infection","volume":"137","author":"Govero","year":"2017","journal-title":"Antivir. Res."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Kim, J.-A., Seong, R.-K., Kumar, M., and Shin, O.S. (2018). Favipiravir and ribavirin inhibit replication of Asian and African strains of zika virus in different cell models. Viruses, 10.","DOI":"10.3390\/v10020072"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Soto-Acosta, R., Jung, E., Qiu, L., Wilson, D., Geraghty, R., and Chen, L. (2021). 4,7-Disubstituted 7H-Pyrrolo[2,3-D]Pyrimidines and Their Analogs As Antiviral Agents Against Zika Virus. Molecules, 26.","DOI":"10.3390\/molecules26133779"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Baz, M., and Boivin, G. (2019). Antiviral agents in development for zika virus infections. Pharmaceuticals, 12.","DOI":"10.3390\/ph12030101"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1016\/j.ijantimicag.2017.08.016","article-title":"The thiopurine nucleoside analogue 6-methylmercaptopurine riboside (6MMPr) effectively blocks Zika virus replication","volume":"50","author":"Franca","year":"2017","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Brzuska, G., Pastuch-Gawolek, G., Krawczyk, M., Szewczyk, B., and Krol, E. (2020). Anti-tick-borne encephalitis virus activity of novel uridine glycoconjugates containing amide or\/and 1,2,3-triazole moiety in the linker structure. Pharmaceuticals, 13.","DOI":"10.3390\/ph13120460"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"113472","DOI":"10.1016\/j.ejmech.2021.113472","article-title":"Synthesis of alkynylated 1,2,4-oxadiazole\/1,2,3-1H-triazole glycoconjugates: Discovering new compounds for use in chemotherapy against lung carcinoma and Mycobacterium tuberculosis","volume":"220","author":"Moura","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"ref_20","first-page":"914","article-title":"Ultrasound-Assisted Synthesis of 1-N-\u03b2-D-Glucopyranosyl-1H-1,2,3-triazole Benzoheterocycles and their Anti-Inflammatory Activities","volume":"24","author":"Assis","year":"2013","journal-title":"J. Braz. Chem. Soc."},{"key":"ref_21","first-page":"1697","article-title":"Inhibition of Zika virus replication by synthetic bis-naphthoquinones","volume":"30","author":"Gonzaga","year":"2019","journal-title":"J. Braz. Chem. Soc."},{"key":"ref_22","first-page":"473","article-title":"S\u00edntese e avalia\u00e7\u00e3o das atividades fotoprotetora, citot\u00f3xica e antiviral contra o Zika virus de derivados triaz\u00f3licos da benzofenona","volume":"42","author":"Lima","year":"2019","journal-title":"Quim. Nova"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"9112","DOI":"10.1002\/slct.201901285","article-title":"Synthesis, Antitumor and Cytotoxic Activity of New Adamantyl O-Acylamidoximes and 3-Aryl-5-Adamantane-1,2,4-Oxadiazole Derivatives","volume":"4","author":"Aguiar","year":"2019","journal-title":"ChemistrySelect"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2522","DOI":"10.1080\/00397911.2018.1509350","article-title":"Focused microwave irradiation-assisted synthesis of N-cyclohexyl-1,2,4-oxadiazole derivatives with antitumor activity","volume":"48","author":"Ferreira","year":"2018","journal-title":"Synth. Commun."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3529","DOI":"10.1055\/s-0034-1378829","article-title":"Synthesis of 2,3-unsaturated alkynyl O-glucosides from tri-O-acetyl-d-glucal by using montmorillonite K-10\/iron(III) chloride hexahydrate with subsequent copper(I)-catalyzed 1,3-dipolar cycloaddition","volume":"47","author":"Melo","year":"2015","journal-title":"Synthesis"},{"key":"ref_26","first-page":"681","article-title":"New strategies for molecular diversification of 2-[Aminoalkyl-(1H-1,2,3-Triazol-1- yl)]-1,4-naphthoquinones using click chemistry","volume":"28","author":"Melo","year":"2017","journal-title":"J. Braz. Chem. Soc."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/j.ejmech.2013.02.038","article-title":"Potent naphthoquinones against antimony-sensitive and -resistant Leishmania parasites: Synthesis of novel \u03b1- And nor-\u03b1-lapachone-based 1,2,3-triazoles by copper-catalyzed azide-alkyne cycloaddition","volume":"63","author":"Pinto","year":"2013","journal-title":"Eur. J. Med. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"104437","DOI":"10.1016\/j.bioorg.2020.104437","article-title":"Antileishmanial activity of 4-phenyl-1-[2-(phthalimido-2-yl)ethyl]-1H-1,2,3-triazole (PT4) derivative on Leishmania amazonensis and Leishmania braziliensis: In silico ADMET, in vitro activity, docking and molecular dynamic simulations","volume":"105","author":"Holanda","year":"2020","journal-title":"Bioorg. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5.6.1","DOI":"10.1002\/cpbi.3","article-title":"Comparative protein structure modeling using MODELLER","volume":"54","author":"Webb","year":"2016","journal-title":"Curr. Protoc. Bioinforma."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1002\/pro.5560020916","article-title":"Verification of protein structures: Patterns of nonbonded atomic interactions","volume":"2","author":"Colovos","year":"1993","journal-title":"Protein Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"W407","DOI":"10.1093\/nar\/gkm290","article-title":"ProSA-web: Interactive web service for the recognition of errors in three-dimensional structures of proteins","volume":"35","author":"Wiederstein","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"ref_32","first-page":"83","article-title":"Assessment of protein models with three-dimensional profiles","volume":"359","author":"Bowie","year":"1992","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1107\/S0021889892009944","article-title":"PROCHECK: A program to check the stereochemical quality of protein structures","volume":"26","author":"Laskowski","year":"1993","journal-title":"J. Appl. Crystallogr."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s10822-013-9644-8","article-title":"Protein and ligand preparation: Parameters, protocols, and influence on virtual screening enrichments","volume":"27","author":"Adzhigirey","year":"2013","journal-title":"J. Comput. Aided. Mol. Des."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5754","DOI":"10.1021\/acs.jcim.0c00326","article-title":"Discovery of New Hydroxyethylamine Analogs against 3CLproProtein Target of SARS-CoV-2: Molecular Docking, Molecular Dynamics Simulation, and Structure-Activity Relationship Studies","volume":"60","author":"Kumar","year":"2020","journal-title":"J. Chem. Inf. Model."},{"key":"ref_36","unstructured":"(2020). Schr\u00f6dinger Release 2020-1: Protein Preparation Wizard; Epik; Prime, S., LLC, New York, NY, 2016; Impact, Schr\u00f6dinger, LLC, New York, NY, 2016; Prime, Schr\u00f6dinger, LLC, New York, NY."},{"key":"ref_37","unstructured":"(2020). Schr\u00f6dinger Release 2020-1: LigPrep, S., LLC, New York, NY."},{"key":"ref_38","unstructured":"(2020). Schr\u00f6dinger Release 2020-1: Epik, S., LLC, New York, NY."},{"key":"ref_39","unstructured":"(2021). Schr\u00f6dinger Release 2020-1: SiteMap, S., LLC, New York, NY."},{"key":"ref_40","unstructured":"(2020). Schr\u00f6dinger Release 2020-1: Glide, S., LLC, New York, NY."},{"key":"ref_41","unstructured":"(2020). Schr\u00f6dinger Release 2020-1: Prime, S., LLC, New York, NY."},{"key":"ref_42","unstructured":"(2020). Schr\u00f6dinger Release 2020-1: Desmond Molecular Dynamics System, D.E.S.R., New York, NY, 2020. Maestro-Desmond Interoperability Tools, Schr\u00f6dinger, New York, NY."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"9954","DOI":"10.1021\/jp003020w","article-title":"Structure and dynamics of the TIP3P, SPC, and SPC\/E water models at 298 K","volume":"105","author":"Mark","year":"2001","journal-title":"J. Phys. Chem. A"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/19\/5869\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:06:08Z","timestamp":1760166368000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/19\/5869"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,28]]},"references-count":43,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["molecules26195869"],"URL":"https:\/\/doi.org\/10.3390\/molecules26195869","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,28]]}}}