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

Verônica da Silva Oliveira; Cláudia Cândida Silva; Johny Wysllas de Freitas Oliveira; Marcelo de Sousa da Silva; Patricia Garcia Ferreira; Fernando de Carvalho da Siva; Vitor Francisco Ferreira; Euzébio Guimarães Barbosa; Cecília Gomes Barbosa; Carolina Borsoi Moraes; Lucio Holanda Gondim de Freitas-Junior; Attilio Converti; Ádley Antonini Neves de Lima

doi:10.1016/j.jddst.2023.104229

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

J Drug Deliv Sci Technol. 2023 Mar:81:104229. doi: 10.1016/j.jddst.2023.104229. Epub 2023 Feb 8.

Authors

Verônica da Silva Oliveira¹, Cláudia Cândida Silva², Johny Wysllas de Freitas Oliveira¹, Marcelo de Sousa da Silva^{1

3}, Patricia Garcia Ferreira⁴, Fernando de Carvalho da Siva⁵, Vitor Francisco Ferreira⁴, Euzébio Guimarães Barbosa¹, Cecília Gomes Barbosa⁶, Carolina Borsoi Moraes^{6

7}, Lucio Holanda Gondim de Freitas-Junior⁶, Attilio Converti⁸, Ádley Antonini Neves de Lima¹

Affiliations

¹ Department of Pharmacy, Health Sciences Center, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, 59012-570, Brazil.
² School of Technology, State University of Amazonas, Manaus, Amazonas, 69065-020, Brazil.
³ Global Health and Tropical Medicine, Institute of Hygiene and Tropical Medicine, NOVA University Lisbon, Lisbon, 1800-166, Portugal.
⁴ Department of Pharmaceutical Technology, Faculty of Pharmacy, Fluminense Federal University, Niterói, Rio de Janeiro, 24241-002, Brazil.
⁵ Institute of Chemistry, Fluminense Federal University, Niterói, Rio de Janeiro, 24020-150, Brazil.
⁶ Department of Microbiology, Institute of Biomedical Sciences, University of Sao Paulo, São Paulo, São Paulo, 05508-900, Brazil.
⁷ Department of Pharmaceutical Sciences, Federal University of São Paulo, São Paulo, São Paulo, 09913-030, Brazil.
⁸ Department of Civil, Chemical and Environmental Engineering, University of Genoa, Pole of Chemical Engineering, via Opera Pia 15, 16145, Genoa, Italy.

Abstract

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 (EC₅₀) 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).

Keywords: Anti-SARS-CoV-2; Antichagasic activity; Inclusion complexes; Naphthoquinone.