The endocannabinoid system(ECS),particularly its signaling pathways and ligands,has garnered considerable interest in recent years.Along with clinical work investigating the ECS’functions,including its role in the de...The endocannabinoid system(ECS),particularly its signaling pathways and ligands,has garnered considerable interest in recent years.Along with clinical work investigating the ECS’functions,including its role in the development of neurological and inflammatory conditions,much research has focused on developing analytical protocols enabling the precise monitoring of the levels and metabolism of the most potent ECS ligands:exogenous phytocannabinoids(PCs)and endogenous cannabinoids(endocannabinoids,ECs).Solid-phase microextraction(SPME)is an advanced,non-exhaustive sample-preparation technique that facilitates the precise and efficient isolation of trace amounts of analytes,thus making it appealing for the analysis of PCs and ECs in complex matrices of plant and animal/human origin.In this paper,we review recent forensic medicine and toxicological studies wherein SPME has been applied to monitor levels of PCs and ECs in complex matrices,determine their effects on organism physiology,and assess their role in the development of several diseases.展开更多
The renewed interest in dimeric salicylates as broad-spectrum anti-inflammatory and antidiabetic agents provided a rationale to investigate the dimerization of the substituted salicylate D9-tetrahydrocannabinolic acid...The renewed interest in dimeric salicylates as broad-spectrum anti-inflammatory and antidiabetic agents provided a rationale to investigate the dimerization of the substituted salicylate D9-tetrahydrocannabinolic acid(THCA-A, 3 a) 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 D9-THC upon heating. However, only the didepsidic dimer 5 activated PPAR-g, the major target of pre-cannabinoids, but strong binding to serum proteins abolished this activity, also shielding it from the action of esterases.展开更多
文摘The endocannabinoid system(ECS),particularly its signaling pathways and ligands,has garnered considerable interest in recent years.Along with clinical work investigating the ECS’functions,including its role in the development of neurological and inflammatory conditions,much research has focused on developing analytical protocols enabling the precise monitoring of the levels and metabolism of the most potent ECS ligands:exogenous phytocannabinoids(PCs)and endogenous cannabinoids(endocannabinoids,ECs).Solid-phase microextraction(SPME)is an advanced,non-exhaustive sample-preparation technique that facilitates the precise and efficient isolation of trace amounts of analytes,thus making it appealing for the analysis of PCs and ECs in complex matrices of plant and animal/human origin.In this paper,we review recent forensic medicine and toxicological studies wherein SPME has been applied to monitor levels of PCs and ECs in complex matrices,determine their effects on organism physiology,and assess their role in the development of several diseases.
基金financial support to the groups in Novara and Naples(PRIN2017,Project 2017WN73PL,bioactivity-directed exploration of thephytocannabinoid chemical space,Italy)
文摘The renewed interest in dimeric salicylates as broad-spectrum anti-inflammatory and antidiabetic agents provided a rationale to investigate the dimerization of the substituted salicylate D9-tetrahydrocannabinolic acid(THCA-A, 3 a) 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 D9-THC upon heating. However, only the didepsidic dimer 5 activated PPAR-g, the major target of pre-cannabinoids, but strong binding to serum proteins abolished this activity, also shielding it from the action of esterases.
