The evaluation of in vitro antichagasic and anti-SARS-CoV-2 potential of inclusion complexes of β- and methyl-β-cyclodextrin with naphthoquinone

The compound 3a,10b-dihydro-1H-cyclopenta[b]naphtho[2,3-d]furan-5,10-dione (IVS320) is a naphthoquinone with antifungal and antichagasic potential, which however has low aqueous solubility. To increase bioavailability, inclusion complexes with β-cyclodextrin (βCD) and methyl-β-cyclodextrin (MβCD) were prepared by physical mixture (PM), kneading (KN) and rotary evaporation (RE), and their in vitro anti-SARS-CoV-2 and antichagasic potential was assessed. The formation of inclusion complexes led to a change in the physicochemical characteristics compared to IVS320 alone as well as a decrease in crystallinity degree that reached 74.44% for the IVS320-MβCD one prepared by RE. The IVS320 and IVS320-MβCD/RE system exhibited anti-SARS-CoV-2 activity, showing half maximal effective concentrations (EC(50)) of 0.47 and 1.22 μg/mL, respectively. Molecular docking simulation suggested IVS320 ability to interact with the SARS-CoV-2 viral protein. Finally, the highest antichagasic activity, expressed as percentage of Tripanosoma cruzi growth inhibition, was observed with IVS320-βCD/KN (70%) and IVS320-MβCD/PM (72%), while IVS320 alone exhibited only approximately 48% inhibition at the highest concentration (100 μg/mL).