Paulownin Triazole-Chloroquinoline Derivative: A Promising Antiviral Candidate Against Chikungunya Virus

Abstract Viral infections, including arboviruses such as chikungunya, zika, dengue, and mayaro fever, remain significant global health and economic challenges, fueled by the emergence and resurgence of mosquito-borne diseases. 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 µM 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.