Cannabichromene (CBC) Shows Matrix-Dependent Thermal Configurational Stability.

The optical purity of cannabichromene (CBC, ) is affected by the matrix in which it is generated by thermolysis from its native carboxylated form (cannabichromenic acid, CBCA, ). Thus, thermolysis at 130 °C caused a marked decrease of the enantiomeric excess (ee), while, under the same conditions, only a modest decrease of optical purity was observed when thermolysis was carried out . To rationalize these puzzling observations, the kinetics of thermal (100 °C) racemization of enantiopure cannabichromene () was evaluated by enantioselective ultrahigh performance liquid chromatography in solvents (decalin and isopropyl alcohol, neat and acidified with TFA) and surfaces (native and silanized borosilicate glass) of complementary polarity.

Identification of Cannabidiolic and Cannabigerolic Acids as MTDL AChE, BuChE, and BACE-1 Inhibitors Against Alzheimer's Disease by In Silico, In Vitro, and In Vivo Studies.

Cannabidiolic (CBDA) and cannabigerolic (CBGA) acids are naturally occurring compounds from Cannabis sativa plant, previously identified by us as dual PPARα/γ agonists. Since the development of multitarget-directed ligands (MTDL) represents a valuable strategy to alleviate and slow down the progression of multifactorial diseases, we evaluated the potential ability of CBDA and CBGA to also inhibit enzymes involved in the modulation of the cholinergic tone and/or β-amyloid production. A multidisciplinary approach based on computational and biochemical studies was pursued on selected enzymes, followed by behavioral and electrophysiological experiments in an AD mouse model.

Stereoselective Shi-type epoxidation with 3-oxo-4,6--benzylidene pyranoside catalysts: unveiling the role of carbohydrate skeletons.

Asymmetric epoxidation represents a hot topic in organic synthesis. In recent years, organocatalysts based on sugar skeletons have been exploited in asymmetric epoxidation to achieve enantiomeric pure epoxides. In this work, two different endocyclic ketones derived from glucose and galactose protected with a 4,6--benzylidene group have been prepared and exploited for Shi-type epoxidation.

A New Glucosyl Flavone with Inhibitory Activity of Cancer Cell Viability and Other Bioactive Constituents from the Traditional Kurdish Plant L.

A new glucosyl flavone, 5,7,2',5'-tetrahydroxyflavone 7--β-d-glucopyranoside, named loeflingiin, together with apigenin 6--glucoside (isovitexin), coumarins citropten and isompinellin, triterpenoids betulin and betulinic acid, and a mixture of phytosterols β-sitosterol, stigmasterol and campesterol were isolated for the first time from the leaves of wild L. () collected in the Iraqi Kurdistan region. The plant is used by local people to treat wounds and as a vulnerary remedy.

PPARα/γ-Targeting Amorfrutin Phytocannabinoids from Aerial Parts of .

An LC-MS/MS-guided analysis of the aerial parts of afforded new phenethyl (amorfrutin)- and alkyl (cannabis)-type phytocannabinoids (six and four compounds, respectively). The structural diversity of the new amorfrutins was complemented by the isolation of six known members and the synthesis of analogues modified on the aralkyl moiety. All of the compounds so obtained were assayed for agonist activity on PPARα and PPARγ nuclear receptors.

Δ-THC Induces Up-Regulation of Glutamatergic Pathway Genes in Differentiated SH-SY5Y: A Transcriptomic Study.

Cannabinoids, natural or synthetic, have antidepressant, anxiolytic, anticonvulsant, and anti-psychotic properties. Cannabidiol (CBD) and delta-9-tetrahydrocannabinol (Δ-THC) are the most studied cannabinoids, but recently, attention has turned towards minor cannabinoids. Delta-8-tetrahydrocannabinol (Δ-THC), an isomer of Δ-THC, is a compound for which, to date, there is no evidence of its role in the modulation of synaptic pathways.

Δ-THC Protects against Amyloid Beta Toxicity Modulating ER Stress In Vitro: A Transcriptomic Analysis.

Alzheimer's disease (AD) represents the most common form of dementia, characterized by amyloid β (Aβ) plaques and neurofibrillary tangles (NFTs). It is characterized by neuroinflammation, the accumulation of misfolded protein, ER stress and neuronal apoptosis. It is of main importance to find new therapeutic strategies because AD prevalence is increasing worldwide.

Identification of a Novel Curcumin Derivative Influencing Notch Pathway and DNA Damage as a Potential Therapeutic Agent in T-ALL.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy considered curable by modern clinical management. Nevertheless, the prognosis for T-ALL high-risk cases or patients with relapsed and refractory disease is still dismal. Therefore, there is a keen interest in developing more efficient and less toxic therapeutic approaches.

Cannabinol: History, Syntheses, and Biological Profile of the Greatest "Minor" Cannabinoid.

Cannabis ( L.) is an outstanding source of bioactive natural products, with more than 150 different phytocannabinoids isolated throughout the decades; however, studies of their bioactivity have historically concentrated on the so-called "big four" [∆-THC (), CBD (), CBG () and CBC ()]. Among the remaining products, which have traditionally been referred to as "minor cannabinoids", cannabinol (CBN, ) stands out for its important repercussions and implications on the global scientific landscape.

Minor Phytocannabinoids: A Misleading Name but a Promising Opportunity for Biomedical Research.

Despite the very large number of phytocannabinoids isolated from Cannabis ( L.), bioactivity studies have long remained focused on the so called "Big Four" [Δ-THC (), CBD (), CBG () and CBC ()] because of their earlier characterization and relatively easy availability via isolation and/or synthesis. Bioactivity information on the chemical space associated with the remaining part of the cannabinome, a set of ca 150 compounds traditionally referred to as "minor phytocannabinoids", is scarce and patchy, yet promising in terms of pharmacological potential.

Rotational constriction of curcuminoids impacts 5-lipoxygenase and mPGES-1 inhibition and evokes a lipid mediator class switch in macrophages.

Polypharmacological targeting of lipid mediator networks offers potential for efficient and safe anti-inflammatory therapy. Because of the diversity of its biological targets, curcumin (1a) has been viewed as a privileged structure for bioactivity or, alternatively, as a pan-assay interference (PAIN) compound. Curcumin has actually few high-affinity targets, the most remarkable ones being 5-lipoxygenase (5-LOX) and microsomal prostaglandin E synthase (mPGES)-1.

Photochemistry of Cannabidiol (CBD) Revised. A Combined Preparative and Spectrometric Investigation.

Cannabis is a plant with an astonishing ability to biosynthesize cannabinoids, and more than 100 molecules belonging to this class have been isolated. Among them in recent years cannabidiol (CBD) has received the interest of pharmacology as the major nonpsychotropic cannabinoid with many potential clinical applications. Although the reactivity of CBD has been widely investigated, only little attention has been given to the possible photodegradation of this cannabinoid, and the data available in the literature are outdated and, in some cases, conflicting.

The Combined Effect of Branching and Elongation on the Bioactivity Profile of Phytocannabinoids. Part I: Thermo-TRPs.

The affinity of cannabinoids for their CB and CB metabotropic receptors is dramatically affected by a combination of α-branching and elongation of their alkyl substituent, a maneuver exemplified by the -pentyl -> α,α-dimethylheptyl (DMH) swap. The effect of this change on other cannabinoid end-points is still unknown, an observation surprising since thermo-TRPs are targeted by phytocannabinoids with often sub-micromolar affinity. To fill this gap, the α,α-dimethylheptyl analogues of the five major phytocannabinoids [CBD (), Δ-THC (), CBG (), CBC () and CBN ()] were prepared by total synthesis, and their activity on thermo-TRPs (TRPV1-4, TRPM8, and TRPA1) was compared with that of one of their natural analogues.

EHP-101 alleviates angiotensin II-induced fibrosis and inflammation in mice.

Some cannabinoids showed anti-inflammatory and antifibrotic activities. EHP-101 is an oral lipidic formulation of the novel non-psychotropic cannabidiol aminoquinone VCE-004.8, which showed antifibrotic activity in murine models of systemic sclerosis induced by bleomycin.

Cannabinoquinones: Synthesis and Biological Profile.

Neutral cannabinoids are oxidatively unstable and are converted into quinone derivatives by atmospheric- and/or chemical oxidative dearomatization. The study of cannabinoquinones has long been plagued by their lability toward additional oxidative degradation, but full substitution of the quinone ring, as well as the introduction of steric hindrance on the alkyl substituent, have provided sufficient stability for a systematic investigation of their bioactivity and for further clinical development. These studies culminated in the discovery of the aminocannabinoquinone VCE-004.

Δ--Tetrahydrocannabinol: Natural Occurrence, Chirality, and Pharmacology.

The -stereoisomers of Δ-THC [(-)- and (+)-] were identified and quantified in a series of low-THC-containing varieties of registered in Europe as fiber hemp and in research accessions of cannabis. While Δ--THC () occurs in cannabis fiber hemp in the concentration range of (-)-Δ--THC [(-)-], it was undetectable in a sample of high-THC-containing medicinal cannabis. Natural Δ--THC () is scalemic (ca.

Biomimetic Approaches to the Synthesis of Natural Disesquiterpenoids: An Update.

Natural disesquiterpenoids represent a small group of secondary metabolites characterized by complex molecular scaffolds and interesting pharmacological profiles. In the last decade, more than 400 new disesquiterpenoids have been discovered and fully characterized, pointing out once more the "" of nature in the design of new compounds. The perfect blend of complex and unique architectures and biological activity has made sesquiterpene dimers an attractive and challenging synthetic target, inspiring organic chemists to find new and biomimetic approaches to replicate the efficiency and the selectivity of natural processes under laboratory conditions.

Cannabitwinol, a Dimeric Phytocannabinoid from Hemp, L., Is a Selective Thermo-TRP Modulator.

Cannabitwinol (CBDD, ), the second member of a new class of dimeric phytocannabinoids in which two units are connected by a methylene bridge, was isolated from a hemp ( L.) industrial extract. The structural characterization of cannabitwinol, complicated by broadening of H NMR signals and lack of expected 2D NMR correlations at room temperature, was fully carried out in methanol- at -30 °C.

Isomeric O-methyl cannabidiolquinones with dual BACH1/NRF2 activity.

Oxidative stress and inflammation in the brain are two key hallmarks of neurodegenerative diseases (NDs) such as Alzheimer's, Parkinson's, Huntington's and multiple sclerosis. The axis NRF2-BACH1 has anti-inflammatory and anti-oxidant properties that could be exploited pharmacologically to obtain neuroprotective effects. Activation of NRF2 or inhibition of BACH1 are, individually, promising therapeutic approaches for NDs.

Anti-inflammatory Activity of Absinthin and Derivatives in Human Bronchoepithelial Cells.

Bitter taste receptors (hTAS2R) are expressed ectopically in various tissues, raising the possibility of a pharmacological exploitation. This seems of particular relevance in airways, since hTAS2Rs are involved in the protection of the aerial tissues from infections and in bronchodilation. The bis-guaianolide absinthin (), one of the most bitter compounds known, targets the hTAS2R46 bitter receptor.

The Oxidation of Phytocannabinoids to Cannabinoquinoids.

Spurred by a growing interest in cannabidiolquinone (CBDQ, HU-313, ) as a degradation marker and alledged hepatotoxic metabolite of cannabidiol (CBD, ), we performed a systematic study on the oxidation of CBD () to CBDQ () under a variety of experimental conditions (base-catalyzed aerobic oxidation, oxidation with metals, oxidation with hypervalent iodine reagents). The best results in terms of reproducibility and scalability were obtained with λ-periodinanes (Dess-Martin periodinane, 1-hydroxy-1λ,2-benziodoxole-1,3-dione (IBX), and SIBX, a stabilized, nonexplosive version of IBX). With these reagents, the oxidative dimerization that plagues the reaction under basic aerobic conditions was completely suppressed.