Mannich-type modifications of (−)-cannabidiol and (−)-cannabigerol leading to new, bioactive derivatives
Abstract (−)-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...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-11-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-45565-7 |
| _version_ | 1827764428955713536 |
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| author | Eszter Boglárka Lőrincz Gergely Tóth Júlia Spolárics Mihály Herczeg Jan Hodek István Zupkó Renáta Minorics Dorottya Ádám Attila Oláh Christos C. Zouboulis Jan Weber Lajos Nagy Eszter Ostorházi Ildikó Bácskay Anikó Borbás Pál Herczegh Ilona Bereczki |
| author_facet | Eszter Boglárka Lőrincz Gergely Tóth Júlia Spolárics Mihály Herczeg Jan Hodek István Zupkó Renáta Minorics Dorottya Ádám Attila Oláh Christos C. Zouboulis Jan Weber Lajos Nagy Eszter Ostorházi Ildikó Bácskay Anikó Borbás Pál Herczegh Ilona Bereczki |
| author_sort | Eszter Boglárka Lőrincz |
| collection | DOAJ |
| description | Abstract (−)-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. |
| first_indexed | 2024-03-11T11:04:18Z |
| format | Article |
| id | doaj.art-5a9a372dc9b844a19bbb1a3fff919b53 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-11T11:04:18Z |
| publishDate | 2023-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-5a9a372dc9b844a19bbb1a3fff919b532023-11-12T12:17:42ZengNature PortfolioScientific Reports2045-23222023-11-0113112010.1038/s41598-023-45565-7Mannich-type modifications of (−)-cannabidiol and (−)-cannabigerol leading to new, bioactive derivativesEszter Boglárka Lőrincz0Gergely Tóth1Júlia Spolárics2Mihály Herczeg3Jan Hodek4István Zupkó5Renáta Minorics6Dorottya Ádám7Attila Oláh8Christos C. Zouboulis9Jan Weber10Lajos Nagy11Eszter Ostorházi12Ildikó Bácskay13Anikó Borbás14Pál Herczegh15Ilona Bereczki16Department of Pharmaceutical Chemistry, University of DebrecenDepartment of Pharmaceutical Chemistry, University of DebrecenDepartment of Pharmaceutical Chemistry, University of DebrecenDepartment of Pharmaceutical Chemistry, University of DebrecenInstitute of Organic Chemistry and Biochemistry of the Czech Academy of ScienceInstitute of Pharmacodynamics and Biopharmacy, University of SzegedInstitute of Pharmacodynamics and Biopharmacy, University of SzegedDepartment of Physiology, Faculty of Medicine, University of DebrecenDepartment of Physiology, Faculty of Medicine, University of DebrecenDepartments of Dermatology, Venereology, Allergology and Immunology, Staedtisches Klinikum Dessau, Brandenburg Medical School Theodor Fontane and Faculty of Health Sciences BrandenburgInstitute of Organic Chemistry and Biochemistry of the Czech Academy of ScienceDepartment of Applied Chemistry, University of DebrecenDepartment of Medical Microbiology, Semmelweis UniversityDepartment of Pharmaceutical Technology, University of DebrecenDepartment of Pharmaceutical Chemistry, University of DebrecenDepartment of Pharmaceutical Chemistry, University of DebrecenDepartment of Pharmaceutical Chemistry, University of DebrecenAbstract (−)-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.https://doi.org/10.1038/s41598-023-45565-7 |
| spellingShingle | Eszter Boglárka Lőrincz Gergely Tóth Júlia Spolárics Mihály Herczeg Jan Hodek István Zupkó Renáta Minorics Dorottya Ádám Attila Oláh Christos C. Zouboulis Jan Weber Lajos Nagy Eszter Ostorházi Ildikó Bácskay Anikó Borbás Pál Herczegh Ilona Bereczki Mannich-type modifications of (−)-cannabidiol and (−)-cannabigerol leading to new, bioactive derivatives Scientific Reports |
| title | Mannich-type modifications of (−)-cannabidiol and (−)-cannabigerol leading to new, bioactive derivatives |
| title_full | Mannich-type modifications of (−)-cannabidiol and (−)-cannabigerol leading to new, bioactive derivatives |
| title_fullStr | Mannich-type modifications of (−)-cannabidiol and (−)-cannabigerol leading to new, bioactive derivatives |
| title_full_unstemmed | Mannich-type modifications of (−)-cannabidiol and (−)-cannabigerol leading to new, bioactive derivatives |
| title_short | Mannich-type modifications of (−)-cannabidiol and (−)-cannabigerol leading to new, bioactive derivatives |
| title_sort | mannich type modifications of cannabidiol and cannabigerol leading to new bioactive derivatives |
| url | https://doi.org/10.1038/s41598-023-45565-7 |
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