Synthesis of cannabidiol-based compounds as ACE2 inhibitors with potential application in the treatment of COVID-19

• Published in: European journal of medicinal chemistry Vol. 260; pp. 115760 - 115769
• Main Authors: Marques, Gabriel Vitor de Lima, Marques, Daisymara Priscila de Almeida, Clarindo, Felipe Alves, Avendaño-Villarreal, Jesus Alberto, Guerra, Fabiana Sélos, Fernandes, Patrícia Dias, dos Santos, Eduardo Nicolau, Gusevskaya, Elena Vitalievna, Kohlhoff, Markus, Moreira, Fabrício de Araújo, Andrade, Luis Adan Flores, Fonseca, Flávio Guimarães da, dos-Reis, Jordana Grazziela Alves Coelho, Oliveira, Renata Barbosa de
• Format: Journal Article
• Language: English
• Published: ISSY-LES-MOULINEAUX Elsevier Masson SAS 15.11.2023; Elsevier
• Subjects: ACE2 inhibitors; Cannabidiol derivatives; Chemistry, Medicinal; COVID-19; Life Sciences & Biomedicine; Pharmacology & Pharmacy; SARS-CoV-2; Science & Technology; COVID-19; ACE2 inhibitors; SARS-CoV-2; Cannabidiol derivatives; CHEMISTRY; DERIVATIVES; BINDING
• ISSN: 0223-5234; 1768-3254; 1768-3254
• DOI: 10.1016/j.ejmech.2023.115760

Cannabis is a general name for plants of the genus Cannabis. Used as fiber, medicine, drug, for religious, therapeutic, and hedonistic purposes along the millenia, it is mostly known for its psychoactive properties. One of its major constituents, cannabidiol (CBD), a non-psychoactive substance, among many other biological activities, has shown potential as an anti-SARS-CoV-2 drug. In this work, three derivatives and an analogue of CBD were synthesized, and cell viability and antiviral activities were evaluated. None of the compounds showed cytotoxicity up to a maximum concentration of 100 μM and, in contrast, displayed a significant antiviral activity, superior to remdesivir and nafamostat mesylate, with IC50 values ranging from 9.4 to 1.9 μM. In order to search for a possible molecular target, the inhibitory activity of the compounds against ACE2 was investigated, with expressive results (IC50 ranging from 3.96 μM to 0.01 μM). [Display omitted] •Cannabidiol has shown potential as an anti-SARS-CoV-2 agent.•Three derivatives and an analogue of cannabidiol were synthesized in this work.•None of the compounds showed cytotoxicity in non-infected VERO cells.•The synthesized compounds showed antiviral IC50 ranging from 9.40–1.90 μM.•The compounds have been shown to act by inhibiting ACE2.