Mannich-type modifications of (-)-cannabidiol and (-)-cannabigerol leading to new, bioactive derivatives.

Autor: Lőrincz EB; Department of Pharmaceutical Chemistry, University of Debrecen, Debrecen, 4032, Hungary.; Doctoral School of Pharmaceutical Sciences, University of Debrecen, Debrecen, 4032, Hungary., Tóth G; Department of Pharmaceutical Chemistry, University of Debrecen, Debrecen, 4032, Hungary., Spolárics J; Department of Pharmaceutical Chemistry, University of Debrecen, Debrecen, 4032, Hungary., Herczeg M; Department of Pharmaceutical Chemistry, University of Debrecen, Debrecen, 4032, Hungary., Hodek J; Institute of Organic Chemistry and Biochemistry of the Czech Academy of Science, Prague, 166 10, Czech Republic., Zupkó I; Institute of Pharmacodynamics and Biopharmacy, University of Szeged, Szeged, 6720, Hungary., Minorics R; Institute of Pharmacodynamics and Biopharmacy, University of Szeged, Szeged, 6720, Hungary., Ádám D; Department of Physiology, Faculty of Medicine, University of Debrecen, Debrecen, 4032, Hungary.; Doctoral School of Molecular Medicine, University of Debrecen, Debrecen, 4032, Hungary., Oláh A; Department of Physiology, Faculty of Medicine, University of Debrecen, Debrecen, 4032, Hungary., Zouboulis CC; Departments of Dermatology, Venereology, Allergology and Immunology, Staedtisches Klinikum Dessau, Brandenburg Medical School Theodor Fontane and Faculty of Health Sciences Brandenburg, 06847, Dessau, Germany., Weber J; Institute of Organic Chemistry and Biochemistry of the Czech Academy of Science, Prague, 166 10, Czech Republic., Nagy L; Department of Applied Chemistry, University of Debrecen, Debrecen, 4032, Hungary., Ostorházi E; Department of Medical Microbiology, Semmelweis University, Budapest, 1089, Hungary., Bácskay I; Department of Pharmaceutical Technology, University of Debrecen, Debrecen, 4032, Hungary., Borbás A; Department of Pharmaceutical Chemistry, University of Debrecen, Debrecen, 4032, Hungary. borbas.aniko@pharm.unideb.hu.; National Laboratory of Virology, Szentágothai Research Centre, Pécs, 7624, Hungary. borbas.aniko@pharm.unideb.hu.; HUN-REN-UD Molecular Recognition and Interaction Research Group, University of Debrecen, Debrecen, 4032, Hungary. borbas.aniko@pharm.unideb.hu., Herczegh P; Department of Pharmaceutical Chemistry, University of Debrecen, Debrecen, 4032, Hungary.; HUN-REN-UD Pharmamodul Research Group, University of Debrecen, Debrecen, 4032, Hungary., Bereczki I; Department of Pharmaceutical Chemistry, University of Debrecen, Debrecen, 4032, Hungary. bereczki.ilona@pharm.unideb.hu.; National Laboratory of Virology, Szentágothai Research Centre, Pécs, 7624, Hungary. bereczki.ilona@pharm.unideb.hu.; HUN-REN-UD Pharmamodul Research Group, University of Debrecen, Debrecen, 4032, Hungary. bereczki.ilona@pharm.unideb.hu.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2023 Nov 10; Vol. 13 (1), pp. 19618. Date of Electronic Publication: 2023 Nov 10.
DOI: 10.1038/s41598-023-45565-7
Abstrakt: (-)-Cannabidiol (CBD) and (-)-cannabigerol (CBG) are two major non-psychotropic phytocannabinoids that have many beneficial biological properties. However, due to their low water solubility and prominent first-pass metabolism, their oral bioavailability is moderate, which is unfavorable for medicinal use. Therefore, there is a great need for appropriate chemical modifications to improve their physicochemical and biological properties. In this study, Mannich-type reaction was used for the synthetic modification of CBD and CBG for the first time, and thus fifteen new cannabinoid derivatives containing one or two tertiary amino groups were prepared. Thereafter the antiviral, antiproliferative and antibacterial properties of the derivatives and their effects on certain skin cells were investigated. Some modified CBD derivatives showed remarkable antiviral activity against SARS-CoV-2 without cytotoxic effect, while synthetic modifications on CBG resulted in a significant increase in antiproliferative activity in some cases compared to the parent compound.
(© 2023. The Author(s).)
Databáze: MEDLINE
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