Cannabis through the looking glass: chemo- and enantio-selective separation of phytocannabinoids by enantioselective ultra high performance supercritical fluid chromatography

By using the Inverted Chirality Columns Approach (ICCA) we have developed an enantioselective UHPSFC method to determine the enantiomeric excess (ee) of (-)-Δ(9)-THC in medicinal marijuana (Bedrocan®). The ee was high (99.73%), but the concentration of the (+)-enantiomer (0.135%) was not negligible, and it is worth a systematic evaluation of bioactivity

Inhibition of Hedgehog-dependent tumors and cancer stem cells by a newly identified naturally occurring chemotype

Hedgehog (Hh) inhibitors have emerged as valid tools in the treatment of a wide range of cancers. Indeed, aberrant activation of the Hh pathway occurring either by ligand-dependent or -independent mechanisms is a key driver in tumorigenesis. The smoothened (Smo) receptor is one of the main upstream transducers of the Hh signaling and is a validated target for the development of anticancer compounds, as underlined by the FDA-approved Smo antagonist Vismodegib (GDC-0449/Erivedge) for the treatment of basal cell carcinoma. However, Smo mutations that confer constitutive activity and drug resistance have emerged during treatment with Vismodegib. For this reason, the development of new effective Hh inhibitors represents a major challenge for cancer therapy. Natural products have always represented a unique source of lead structures in drug discovery, and in recent years have been used to modulate the Hh pathway at multiple levels. Here, starting from an in house library of natural compounds and their derivatives, we discovered novel chemotypes of Hh inhibitors by mean of virtual screening against the crystallographic structure of Smo. Hh functional based assay identified the chalcone derivative 12 as the most effective Hh inhibitor within the test set. The chalcone 12 binds the Smo receptor and promotes the displacement of Bodipy-Cyclopamine in both Smo WT and drug-resistant Smo mutant. Our molecule stands as a promising Smo antagonist able to specifically impair the growth of Hh-dependent tumor cells in vitro and in vivo and medulloblastoma stem-like cells and potentially overcome the associated drug resistance

Chirality effects on the IRMPD spectra of basket resorcinarene/nucleoside complexes

The IRMPD spectra of the ESI-formed proton-bound complexes of the R,R,R,R- and S,S,S,S-enantiomers of a bis(diamido)-bridged basket resorcin[4]arene (R and S) with cytosine (1), cytidine (2), and cytarabine (3) were measured in the region 2800– 3600 cm1. Comparison of the IRMPD spectra with the corresponding ONIOM (B3LYP/6-31(d):UFF)-calculated absorption frequencies allowed the assessment of the vibrational modes that are responsible for the observed spectroscopic features. All of the complexes investigated, apart from [R·H·3]+, showed similar IRMPD spectra, which points to similar structural and conformational landscapes. Their IRMPD spectra agree with the formation of several isomeric structures in the ESI source, wherein the N(3)-protonated guest establishes noncovalent interactions with the host amidocarbonyl groups that are either oriented inside the host cavity or outside it between one of the bridged side-chains and the upper aromatic nucleus. The IRMPD spectrum of the [R·H·3]+ complex was clearly different from the others. This difference is attributed to the effect of intramolecular hydrogen bonding interactions between the C(2’)-OH group and the aglycone oxygen atom of the nucleosidic guest upon repulsive interactions between the same oxygen atom and the aromatic rings of the host

Enantioseparation on Riboflavin Derivatives Chemically Bonded to Silica Gel as Chiral Stationary Phases for HPLC

International audienceAcetylated and/or 3,5-dimethylphenylcarbamated riboflavins were prepared and the resulting riboflavin derivatives as well as natural riboflavin were regioselectively immobilized on silica gel through chemical bonding at the 5’-O- or 3-N-position of the riboflavin to develop novel chiral stationary phases (CSPs) for enantioseparation by high-performance liquid chromatography (HPLC). The chiral recognition abilities of the obtained CSPs were significantly dependent on the structures of the riboflavin derivatives, the position of the chemical bonding on the silica gel, and the structures of the racemic compounds. The CSPs bonded at the 5’-O-position on the silica gel tended to well separate helicene derivatives, while the CSPs bonded at the 3-N-position composed of acetylated and 3,5-dimethylphenylcarbamated riboflavins showed a better resolving ability toward helicene derivatives and bulky aromatic racemic alcohols, respectively, and some of them were completely separated into the enantiomers. The observed difference in the chiral recognition abilities of these riboflavin-based CSPs is discussed based on the difference in their structures, including the substituents of riboflavin and the positions immobilized on the silica gel

Dynamic HPLC on chiral stationary phases: a powerful tool for the investigation of stereomutation processes

Dynamic HPLC on enantioselective stationary phases has become a well-established technique to investigate chiral molecules with internal motions that result in stereoinversion and occur on the time scale of the separation process. Kinetic parameters for the on-column interconversion phenomena can be extracted from experimental peak profiles by computer simulation or by direct calculation methods. The technique has been used in a wide range of temperatures and is complementary in scope to dynamic NMR spectroscopy

New Psychoactive Substances Toxicity: A Systematic Review of Acute and Chronic Psychiatric Effects

New psychoactive substances (NPSs) are a heterogenous group of psychotropic molecules and diverted pharmaceutical drugs sold worldwide as legal substitutes for controlled drugs. The psychiatric consequences of NPS use are relatively unknown, although evidence of related psychotic symptoms has been described in the literature. We sought to summarize the available evidence on NPS-related psychiatric disorders, to facilitate the interpretation of the molecular mechanism underlying their specific pathologies. A literature search of Scopus, PubMed and Google Scholar was conducted including studies published between 2013 and 2024, in which a correlation between NPS consumption and psychiatric symptoms was reported. Furthermore, the short- and long-term psychopathological effects were included. The literature search resulted in 109 NPS-related intoxication cases in which acute or chronic psychiatric symptoms were reported, mostly related to synthetic cannabinoids, followed by synthetic cathinones, hallucinogens, natural NPSs and stimulants. The most common acute symptoms were hallucinations, aggressiveness, and psychotic and bizarre behavior, related to the molecular disbalance of neurotransmitters in the central nervous systems, with different mechanisms. The lack of clear diagnostic criteria and toxicological analyses has resulted in crucial complications in psychiatric diagnoses related to NPS intoxication. Hence, the implementation of toxicological screening procedures in emergency rooms, including the main NPS classes, should support the diagnosis of acute intoxication and its proper therapeutic treatment. Finally, proper follow-up should be implemented to assess the chronic sequelae

The Enantiopure 1,2-Diphenylethylenediamine (DPEDA) Motif in the Development of Organocatalysts for Asymmetric Reactions: Advances in the Last 20 Years

1,2-Diphenylethylenediamine (DPEDA) is a privileged chiral scaffold being used in the construction of a broad variety of organocatalysts and ligands for enantioselective organic reactions. This molecule gave a significant contribution in the synthesis of structurally different bi/multifunctional organocatalysts. DPEDA played an essential role in the development of organocatalysts capable of yielding important information on the different reaction mechanisms, like enamine, iminium, hydrogen-bonding and anion-binding catalysis. The aim of the present review is to highlight and summarize the achievements reached in the last 20 years (2004–2024) in the chemistry of DPEDA-based organocatalysts for asymmetric synthesis

Phytochemical studies and antioxidant activity of two South African medicinal plants traditionally used for the management of opportunistic fungal infections in HIV/AIDS patients

<p>Abstract</p> <p>Background</p> <p>It has been observed that perturbations in the antioxidant defense systems, and consequently redox imbalance, are present in many tissues of HIV-infected patients. Hence, the exogenous supply of antioxidants, as natural compounds that scavenge free radicals, might represent an important additional strategy for the treatment of HIV infection. The aim of this study was therefore to analyse the phytochemical constituents and antioxidant potential of <it>Gasteria bicolor </it>Haw and <it>Pittosporum viridiflorum </it>Sims., two South African plants traditionally used for the management of opportunistic fungal infections (OFIs) in AIDS patients.</p> <p>Methods</p> <p>The <it>in vitro </it>antioxidant properties of the two plants were screened through DPPH (1,1-diphenyl-2-picrylhydrazyl), NO (nitric oxide), H₂O₂(hydrogen peroxide) radical scavenging effects and reducing power assays. Phytochemical studies were done by spectrophotometric techniques.</p> <p>Results</p> <p>There were no significant differences in the flavonoid and proanthocyanidins contents between the leaves and bark extracts of <it>Gasteria bicolor </it>and <it>Pittosporum viridiflorum </it>respectively, while the total phenolic content of the bark extract of <it>P. viridiflorum </it>was significantly higher than that of <it>G. bicolor </it>leaf. The acetone extracts of both plants indicated strong antioxidant activities.</p> <p>Conclusion</p> <p>The results from this study indicate that the leaves and stem extracts of <it>Gasteria bicolor </it>and <it>Pittosporum viridiflorum </it>respectively possess antioxidant properties and could serve as free radical inhibitors, acting possibly as primary antioxidants. Since reactive oxygen species are thought to be associated with the pathogenesis of AIDS, and HIV-infected individuals often have impaired antioxidant defenses, the inhibitory effect of the extracts on free radicals may partially justify the traditional use of these plants in the management of OFIs in HIV patients in South Africa.</p

Il ruolo della cromatografia enantioselettiva nello sviluppo di farmaci chirali

Farmaci chirali - racemati e singoli enantiomer