Pesquisa | SciELO

Chikungunya virus (CHIKV) is a re-emerging disease caused by an alphavirus of the Togaviridae family. Since its first description in 1952, the disease has spread worldwide, affecting populations in both tropical and temperate countries. To date, there is no licensed vaccine or specific pharmacological treatment. Therefore, there is an increasing urgency in developing new antiviral drugs capable of specifically inhibiting viral replication. In the present work, we report the synthesis and antiviral activity evaluation of nineteen naphthoquinone derivatives, containing a sulfonamide or sulfonate group. Cell viability assays indicated a low toxic potential for all tested compounds and inhibitory assays against CHIKV identified five compounds with potent activity. The compounds were also evaluated for their virucidal potential, and the results demonstrated that compound 11a exhibited a virucidal effect higher than 70% in the treatment with 20 µM. Furthermore, in silico studies were performed to predict the antiviral drug targets.

Furanaphthoquinones are well known in medicinal chemistry for exhibiting relevant structural heterogeneity and bioactivities. In this work, it was synthesized a series of furanaphthoquinones through a tandem reaction between lawsone (8) and cyclic ketones in the presence of morpholine. This strategy provides an efficient and general method for synthesizing furanaphthoquinones with activity against the epimastigote form of Trypanosoma cruzi (T. cruzi), the parasite that causes Chagas disease. Compound 9b was the better prototype, and it exhibited high potency for causing parasite death, showed reduced acute toxicity towards mammalian cells, and was capable of rupturing the epimastigote plasma membrane and acting on sterol 14α-demethylase (CYP51). Additionally, 9b reduced trypomastigote viability by 99% after 24 h. Candidate 9b demonstrated the best and most promising profile when bound to CYP51.

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