The evaluation of in vitro antichagasic and anti-SARS-CoV-2 potential of inclusion complexes of I3-and methyl-I3-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 bioavail-ability, inclusion complexes with I3-cyclodextrin (I3CD) and methyl-I3-cyclodextrin (MI3CD) 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-MI3CD one prepared by RE. The IVS320 and IVS320-MI3CD/RE system exhibited anti-SARS-CoV-2 ac-tivity, showing half maximal effective concentrations (EC50) of 0.47 and 1.22 mu g/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-I3CD/KN (70%) and IVS320-MI3CD/PM (72%), while IVS320 alone exhibited only approximately 48% inhibition at the highest concentration (100 mu g/mL).

Automated summary

The compound IVS320 was studied for its antifungal and antichagasic potential, but it has low aqueous solubility. To improve bioavailability, inclusion complexes with I3-cyclodextrin and methyl-I3-cyclodextrin were prepared using different methods. The inclusion complexes showed changes in physicochemical characteristics and decreased crystallinity compared to IVS320 alone. The IVS320 and IVS320-MI3CD/RE system exhibited anti-SARS-CoV-2 activity, and IVS320 showed interactions with the viral protein. The highest antichagasic activity was observed with IVS320-I3CD/KN and IVS320-MI3CD/PM.