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Natural products, especially plant-derived compounds, have been crucial in drug discovery and often serve as scaffolds for synthetic drug development. This study focused on modifying paulownin, an isolated lignan, through a Click reaction to incorporate 1,2,3-triazole and quinolinic ring frameworks. The resulting derivative 7 was evaluated for its in vitro antiviral activity against Alphavirus chikungunya (CHIKV). The paulownin derivative 7 did not exhibit cytotoxicity in Vero cells and demonstrated potent activity against CHIKV, with median effective concentration value of 9.05\u00a0\u00b5M and a selectivity index exceeding 16.8. Furthermore, compound 7 outperformed positive controls, being over 46 times more active against CHIKV. Cytopathic effect assays confirmed this anti-CHIKV activity. The virucidal assay indicated that the compound does not exert a direct effect on CHIKV particles before cell infection. RT-qPCR studies further demonstrated derivative 7 significantly reduces CHIKV replication. These findings highlight the paulownin derivative 7 as a promising and selective candidate for CHIKV treatment.<\/jats:p>","DOI":"10.1093\/lambio\/ovaf092","type":"journal-article","created":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T07:50:38Z","timestamp":1751529038000},"source":"Crossref","is-referenced-by-count":3,"title":["Paulownin triazole-chloroquinoline derivative: a promising antiviral candidate against chikungunya virus"],"prefix":"10.1093","volume":"78","author":[{"given":"Adriana Cotta Cardoso","family":"Reis","sequence":"first","affiliation":[{"name":"Federal University of Ouro Preto Pharmacy School, Department of Pharmacy, , Ouro Preto, MG 35402-163 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila Mendes","family":"de\u00a0Oliveira","sequence":"additional","affiliation":[{"name":"Pontifical Catholic University of Minas Gerais Department of Physics and Chemistry, , Belo Horizonte, MG 30535-901 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