The dimerization of Δ 9 -tetrahydrocannabinolic acid A (THCA-A).
| Autor: | Cuadari A; Dipartimento di Scienze del Farmaco, Università del Piemonte Orientale, Novara 28100, Italy., Pollastro F; Dipartimento di Scienze del Farmaco, Università del Piemonte Orientale, Novara 28100, Italy., Unciti-Broceta JD; Emerald Health Biotechnology España, Calle Cecilia Payne, Córdoba 14014, Spain., Caprioglio D; Dipartimento di Scienze del Farmaco, Università del Piemonte Orientale, Novara 28100, Italy., Minassi A; Dipartimento di Scienze del Farmaco, Università del Piemonte Orientale, Novara 28100, Italy., Lopatriello A; Dipartimento di Farmacia, Università di Napoli Federico II, Napoli 80131, Italy., Muñoz E; Maimonides Biomedical Research Institute of Córdoba, Cordoba 14004, Spain.; Department of Cellular Biology, Physiology and Immunology, University of Córdoba, Cordoba 14004, Spain.; University Hospital Reina Sofía, Avenida de Menendez Pidal s/n, Cordoba 14004, Spain., Taglialatela-Scafati O; Dipartimento di Farmacia, Università di Napoli Federico II, Napoli 80131, Italy., Appendino G; Dipartimento di Scienze del Farmaco, Università del Piemonte Orientale, Novara 28100, Italy. |
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| Jazyk: | angličtina |
| Zdroj: | Acta pharmaceutica Sinica. B [Acta Pharm Sin B] 2019 Sep; Vol. 9 (5), pp. 1078-1083. Date of Electronic Publication: 2019 Jun 24. |
| DOI: | 10.1016/j.apsb.2019.06.007 |
| Abstrakt: | The renewed interest in dimeric salicylates as broad-spectrum anti-inflammatory and anti-diabetic agents provided a rationale to investigate the dimerization of the substituted salicylate Δ 9 -tetrahydrocannabinolic acid (THCA-A, 3a ) as a strategy to solve its instability to decarboxylation and to generate analogues and/or pro-drugs of this native pre-cannabinoid. Activation of the carboxylic group with the DCC-HOBt-DMAP protocol afforded a high yield of the OBt ester 4 , that was next converted into the highly crystalline di-depsidic dimer 5 upon treatment with DMAP. The mono-depsidic dimer 6 was also formed when the reaction was carried out with partially decarboxylated THCA-A samples. The structure of the depsidic dimers was established by spectroscopic methods and by aminolysis of 5 into the pre-cannabinoid amide 7 . Both dimers showed excellent shelf stability and did not generate significant amounts of Δ 9 -THC upon heating. However, only the didepsidic dimer 5 activated PPAR- γ , the major target of pre-cannabinoids, but strong binding to serum proteins abolished this activity, also shielding it from the action of esterases. (© 2019 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.) |
| Databáze: | MEDLINE |
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