Autor(es):
Oliveira, Verônica da Silva ; Silva, Cláudia Cândida ; de Freitas Oliveira, Johny Wysllas ; da Silva, Marcelo de Sousa ; Ferreira, Patricia Garcia ; da Siva, Fernando de Carvalho ; Ferreira, Vitor Francisco ; Barbosa, Euzébio Guimarães ; Barbosa, Cecília Gomes ; Moraes, Carolina Borsoi ; Freitas-Junior, Lucio Holanda Gondim de ; Converti, Attilio ; Lima, Ádley Antonini Neves de
Data: 2023
Identificador Persistente: http://hdl.handle.net/10362/154978
Origem: Repositório Institucional da UNL
Assunto(s): Anti-SARS-CoV-2; Antichagasic activity; Inclusion complexes; Naphthoquinone; RM Therapeutics. Pharmacology; QR355 Virology; QR Microbiology; RA Public aspects of medicine; RA0421 Public health. Hygiene. Preventive Medicine; Infectious Diseases; Pharmaceutical Science; Biochemistry, Genetics and Molecular Biology (miscellaneous); Parasitology; Virology; SDG 3 - Good Health and Well-being; SDG 9 - Industry, Innovation, and Infrastructure
Descrição
Funding Information: The authors thank the Coordination for the Improvement of Higher Education Personnel (CAPES) and the National Council for Scientific and Technological Development (CNPq) for their financial support. This study was supported by the CAPES — number 88887.505029/2020–00 . Cecilia Gomes Barbosa receives a scholarship funded by CAPES — number 88887.643352/2021–00 . Publisher Copyright: © 2023 Elsevier B.V.
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).
