Structural modification of natural and synthetic quinones for antiviral screening against human important...

Arboviruses such as dengue and Zika are clinically significant human pathogens lacking effective antiviral treatments. Studies seeking DENV inhibitors, consider lipophilicity as a crucial parameter for optimising drug entry into infected host cells. In this study, Aloesaponarin I (1), Aloe-Emodin (2), obtained from Aloe vera roots, together with Methylnaphthazarin (3) were derivatized to increase lipophilicity, by acylation and alkylation reactions. The derivatives obtained were evaluated for antiviral activity against all four DENV serotypes and ZIKV in vitro using the Focus Reduction Neutralisation Test and Celgosivir and human sera as positive controls. Additionally, cytotoxic studies were performed showed that derivatives from (1) and (2) were non-toxic at 250-1.9 µM, while (3) derivatives from 156-7.8 µM. Derivatives as 10, 19 and 24 had the maximum inhibition percentages ranged from 82 to 99% with IC₅₀ values between 18 to 1 µM, mainly against DENV4 and Zika viruses.