{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T05:15:56Z","timestamp":1788412556723,"version":"build-2803163510"},"reference-count":45,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Brazilian agencies Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico"},{"id":[{"id":"https:\/\/ror.org\/03swz6y49","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004586","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior (CAPES), Brazil"},{"id":[{"id":"https:\/\/ror.org\/00x0ma614","id-type":"ROR","asserted-by":"publisher"}]},{"name":"National Institutes of Science and Technology Program (INCT) on Diseases of Neglected Populations","award":["465313\/2014-0"],"award-info":[{"award-number":["465313\/2014-0"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The persistent global threat posed by emerging and re-emerging RNA viruses, including SARS-CoV-2, influenza A(H1N1)pdm09, DENV-2, and CHIKV, highlights the critical need for novel and broad-spectrum antiviral agents. Building upon the established antiviral activity of the quinoline scaffold, this study employed a molecular hybridization strategy to design and synthesize a novel series of 1,2,3-triazole\u2013quinoline derivatives (compounds 4a\u20134h). This approach strategically fused the bioactive quinoline nucleus with the pharmaceutically favorable 1,2,3-triazole ring. The new compounds were synthesized efficiently in three steps with moderate-to-high yields, and their structures were subsequently determined. Their inhibitory capacities against the four viruses and cytotoxicity across relevant cell lines were evaluated in vitro. The initial screening demonstrated that compounds 4a\u20134h possessed broad-spectrum antiviral activity, showing high inhibition percentages at 10 \u00b5M against SARS-CoV-2, DENV-2, and CHIKV. Notably, compounds 4c and 4e, substituted with methoxy and ethyl groups, respectively, displayed exceptional potency and safety against SARS-CoV-2, yielding high selectivity indices (SI: 1896.5 and 1265.8, respectively). Furthermore, in silico absorption, distribution, metabolism, and excretion (ADME) and molecular docking calculations suggested favorable drug-likeness profiles, including improved lipophilicity and non-P-glycoprotein substrate feasibility. The findings validate the molecular hybridization strategy, establishing this new class of compounds as promising, multi-target antiviral prototypes for further preclinical exploration against prevalent viral pathogens.<\/jats:p>","DOI":"10.3390\/v18090951","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T12:41:18Z","timestamp":1788266478000},"page":"951","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Synthesis and Broad-Spectrum Antiviral Evaluation of Novel 1,2,3-Triazole\u2013Quinoline Derivatives Targeting SARS-CoV-2, Influenza, DENV-2, and CHIKV"],"prefix":"10.3390","volume":"18","author":[{"given":"Alcione Silva","family":"de Carvalho","sequence":"first","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Aplicadas a Produtos para a Sa\u00fade, Faculdade de Farm\u00e1cia, Universidade Federal Fluminense, Niter\u00f3i 24241-000, RJ, 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