Synthetic bioactive olivetol-related amides: The influence of the phenolic group in cannabinoid receptor activity

Brizzi, Antonella; Aiello, Francesca; Boccella, Serena; Cascio, Maria Grazia; Petrocellis, Luciano De; Frosini, Maria; Gado, Francesca; Ligresti, Alessia; Luongo, Livio; Marini, Pietro; Mugnaini, Claudia; Pessina, Federica; Corelli, Federico; Maione, Sabatino; Manera, Clementina; Pertwee, Roger Guy; Marzo, Vincenzo Di

doi:10.1016/j.bmc.2020.115513

Cited by 4 publications

(3 citation statements)

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“…Binding at equilibrium was performed as previously reported. , Briefly, membranes from HEK-293 cells overexpressing the respective human recombinant CB1R ( B max = 2.5 pmol/mg protein) and human recombinant CB2R ( B max = 11.4 pmol/mg protein) were incubated with [ 3 H]-CP-55,940 (0.14 nM/ K d = 0.18 nM and 0.53 nM/ K d = 5.89 nM, respectively, for CB1R and CB2R) as the high-affinity ligand. Competition curves were performed by displacing [ 3 H]-CP-55,940 with increasing concentration of compounds (0.1–10 μM).…”

Section: Methodsmentioning

confidence: 99%

“…The exploration of novel AChE-I and their hybrids with other enzyme inhibitors (e.g., MAO A and B), − as well as potent and selective ligands of the cannabinoid receptors, − has long been a major activity of our research groups. Consequently, the aim of this work was the design, synthesis, and physicochemical/pharmacological profiling at the preclinical level of new dual-acting molecules that can inhibit the enzyme AChE and modulate the CB2R.…”

Section: Introductionmentioning

confidence: 99%

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Novel Dual-Acting Hybrids Targeting Type-2 Cannabinoid Receptors and Cholinesterase Activity Show Neuroprotective Effects In Vitro and Amelioration of Cognitive Impairment In Vivo

Mugnaini,

Brizzi,

Paolino

et al. 2024

ACS Chem. Neurosci.

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Alzheimer's disease (AD) is a neurodegenerative form of dementia characterized by the loss of synapses and a progressive decline in cognitive abilities. Among current treatments for AD, acetylcholinesterase (AChE) inhibitors have efficacy limited to symptom relief, with significant side effects and poor compliance. Pharmacological agents that modulate the activity of type-2 cannabinoid receptors (CB2R) of the endocannabinoid system by activating or blocking them have also been shown to be effective against neuroinflammation. Herein, we describe the design, synthesis, and pharmacological effects in vitro and in vivo of dual-acting compounds that inhibit AChE and butyrylcholinesterase (BChE) and target CB2R. Within the investigated series, compound 4g proved to be the most promising. It achieved IC 50 values in the low micromolar to submicromolar range against both human cholinesterase isoforms while antagonizing CB2R with K i of 31 nM. Interestingly, 4g showed neuroprotective effects on the SH-SY5Y cell line thanks to its ability to prevent oxidative stress-induced cell toxicity and reverse scopolamine-induced amnesia in the Y-maze forced alternation test in vivo.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Novel Dual-Acting Hybrids Targeting Type-2 Cannabinoid Receptors and Cholinesterase Activity Show Neuroprotective Effects In Vitro and Amelioration of Cognitive Impairment In Vivo

Mugnaini,

Brizzi,

Paolino

et al. 2024

ACS Chem. Neurosci.

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“…This compound leads to the different cannabinoids, including CBD becoming an important metabolite in cannabinoid biosynthesis [30]. In fact, it is used in various methods to produce synthetic analogues of cannabinoids [31]. Chemically, OLV structure is found in cannabinoids, so OLV could be used as an analogue of CBD as it could mimic its interactions with the drug delivery systems.…”

Section: Introductionmentioning

confidence: 99%