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Therefore, there is a great need for appropriate chemical modifications to improve their physicochemical properties. Incorporation of fluorine atom(s) at appropriate positions often improves the metabolic stability of the parent compound, increasing its bioavailability, and enhances its binding affinity to therapeutic targets, making fluorine a highly valuable element in modern drug development. Furthermore, amino functional groups may improve the water solubility and bioavailability of the compounds. Building on these principles, our strategy focused on introducing groups containing mono-, di-, and trifluoroethylamine or fluorinated aniline moieties into cannabinoids to improve their pharmacokinetic and pharmacological profiles.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Mannich-type reaction was applied, using commercially available 2-fluoroethylamine, 2,2-difluoroethylamine, 2,2,2-trifluoroethylamine, 3-fluoroaniline and 4-fluoroaniline as reagents. One or two oxazine rings with fluorine-containing side chains were condensed to the aromatic core of the cannabinoids, and the formation of mono- or disubstituted derivatives was controlled by the appropriate choice of reaction conditions. The biological activity of the derivatives was investigated in various relevant fields.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results and conclusion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s42238-026-00403-1","type":"journal-article","created":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T14:56:06Z","timestamp":1770303366000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Design, synthesis, and biological profiling of fluorinated cannabidiol and cannabigerol derivatives as promising therapeutic agents"],"prefix":"10.1186","volume":"8","author":[{"given":"Ferenc D\u00e1niel","family":"Petr\u00f3czi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ang\u00e9la","family":"T\u00f3tik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikl\u00f3s","family":"Bege","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f3zsef","family":"Kir\u00e1ly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erzs\u00e9bet","family":"Szab\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zsuzsanna","family":"Szab\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikoletta","family":"Dobos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rasha Ghanem","family":"Kattoub","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charu","family":"Upadhyay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eszter","family":"Ostorh\u00e1zi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Hodek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Weber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f3zsef","family":"Arany","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorottya","family":"\u00c1d\u00e1m","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christos C.","family":"Zouboulis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Attila","family":"Ol\u00e1h","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Istv\u00e1n","family":"Bajza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1rp\u00e1d","family":"T\u00f3saki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00e1bor","family":"Halmos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brijesh","family":"Rathi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u00e1l","family":"Herczegh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anik\u00f3","family":"Borb\u00e1s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilona","family":"Bereczki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,5]]},"reference":[{"issue":"1","key":"403_CR1","doi-asserted-by":"publisher","first-page":"75","DOI":"10.5863\/1551-6776-25.1.75","volume":"25","author":"R Abu-Sawwa","year":"2020","unstructured":"Abu-Sawwa R, Stehling C. 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