Design, synthesis, and biological profiling of fluorinated cannabidiol and cannabigerol derivatives as promising therapeutic agents
Our findings indicate that aliphatic modifications positively influence pharmacokinetic parameters, including absorption, in contrast to aromatic groups, which increase lipophilicity and lead to decreased bioavailability. Among the modifications, the monosubstituted derivatives containing a single oxazine ring with an aliphatic fluorine-containing side chain, especially the mono- and trifluoroethyl moieties, proved to be the most promising. These modifications appeared particularly advantageous in the CBG series compared to the properties of the CBG parent compound. This may suggest that the presence of a phenolic OH group is beneficial for biological activity. Some of the derivatives showed anticancer potential against various tumor cell lines, while others modulated sebaceous lipogenesis, and certain compounds exhibited a notable antimalarial effect.
Authors
- Zsuzsanna Szabó (ORCID: https://orcid.org/0000-0003-4838-4210)
- Ilona Bereczki (ORCID: https://orcid.org/0000-0003-4601-7257)
- Christos C. Zouboulis (ORCID: https://orcid.org/0000-0003-1646-2608)
- Nikoletta Dobos (ORCID: https://orcid.org/0000-0003-1750-0071)
- Attila Oláh (ORCID: https://orcid.org/0000-0003-4122-5639)
- István Bajza
- József Király
- Charu Upadhyay
- Brijesh Rathi (ORCID: https://orcid.org/0000-0003-2133-8847)
- Pál Herczegh (ORCID: https://orcid.org/0000-0003-4265-5518)
- Rasha Ghanem Kattoub (ORCID: https://orcid.org/0009-0002-4896-4880)
- Dorottya Ádám (ORCID: https://orcid.org/0000-0002-3543-4146)
- Árpád Tósaki (ORCID: https://orcid.org/0000-0002-3510-4390)
- Miklós Bege (ORCID: https://orcid.org/0000-0002-2424-4523)
- József Arany (ORCID: https://orcid.org/0000-0003-1976-1216)
- Jan Hodek (ORCID: https://orcid.org/0000-0001-7677-9354)
- Ferenc Dániel Petróczi (ORCID: https://orcid.org/0009-0005-9704-4599)
- Gábor Halmos
- Angéla Tótik
- Anikó Borbás
- Jan Weber
- Erzsébet Szabó
Institutions
- Semmelweis University (HU)
- University of Delhi (IN)
- University of Debrecen (HU)
- Debrecen Reformed Theological University (HU)
- Städtisches Klinikum Dessau (DE)
- Institute of Organic Chemistry (PL)
- Medizinische Hochschule Brandenburg Theodor Fontane (DE)
- Czech Academy of Sciences, Institute of Organic Chemistry and Biochemistry (CZ)
- University of Pecs (HU)
Publication Details
- Journal
- Journal of Cannabis Research
- Published
- 2026-02-05
- DOI
- https://doi.org/10.1186/s42238-026-00403-1
- Primary Topic
- Cannabis and Cannabinoid Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- European Commission
- Magyar Tudományos Akadémia
- Debreceni Egyetem
- Innovációs és Technológiai Minisztérium
- European Regional Development Fund
- Nemzeti Kutatási, Fejlesztési és Innovaciós Alap
- National Research, Development and Innovation Office