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Quinoline-based compounds have emerged as promising scaffolds for antiviral drug development. In this study, five 4-amino-7-chloroquinoline derivatives were synthesized and evaluated for their in vitro antiviral activity against CHIKV, ZIKV, and MAYV in Vero cells. Cytotoxicity and antiviral effects were assessed using a tetrazolium-based assay, followed by complementary analyses including cytopathic effect inhibition, virucidal assay, and viral load quantification by RT-qPCR. Among the tested compounds, derivative\n                    <jats:bold>6<\/jats:bold>\n                    demonstrated the most pronounced anti-CHIKV activity, with a low micromolar effective concentration and moderate selectivity index. This compound significantly reduced viral replication, preserved cell monolayer integrity, and decreased viral titers, achieving substantial viral load reduction confirmed by RT-qPCR. No virucidal activity was observed. In contrast, compound\n                    <jats:bold>6<\/jats:bold>\n                    inhibited the virus-induced cytopathic effect when administered after viral adsorption, suggesting that its antiviral activity is unlikely to result from interference with viral attachment or adsorption but rather from inhibition of a post-adsorption stage of the viral replication cycle. Overall, these findings highlight 4-amino-7-chloroquinoline derivatives as a promising class of antiviral agents and identify compound\n                    <jats:bold>6<\/jats:bold>\n                    as a potential lead candidate for further development against CHIKV.\n                  <\/jats:p>","DOI":"10.1007\/s00284-026-05133-4","type":"journal-article","created":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T05:51:45Z","timestamp":1787377905000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of 4-Amino-7-chloroquinoline Derivative with In Vitro Activity Against Chikungunya Virus"],"prefix":"10.1007","volume":"83","author":[{"given":"Adriana Cotta Cardoso","family":"Reis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila","family":"Portruneli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00edvia","family":"da Cunha Agostini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila Rezende","family":"Minelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luana Neves","family":"Dias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adalberto Jos\u00e9","family":"de Lima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Breno","family":"de Mello Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00edntia Lopes","family":"de Brito Magalh\u00e3es","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glenda Nicioli","family":"da Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guilherme Rocha","family":"Pereira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geraldo C\u00e9lio","family":"Brand\u00e3o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,22]]},"reference":[{"key":"5133_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fmicb.2021.773211","volume":"12","author":"M Viglietta","year":"2021","unstructured":"Viglietta M, Bellone R, Blisnick AA, Failloux AB (2021) Vector specificity of arbovirus transmission. 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