Antifungal and Antiproliferative Activity of Pistagremic Acid and Flavonoids Extracted from the Galls of Pistacia chinensis subsp. integerrima.

Pistacia chinensis subsp. integerrima (J.L. Stewart) Rech. f. is a plant known for its therapeutic applications in traditional medicine, which are related to its antimicrobial, anticancer, antioxidant, anti-inflammatory, analgesic, antidiarrheal, and muscle relaxant properties. The galls of P. chinensis are rich in triterpenes and flavonoids, and we here report the extraction of pistagremic acid (1), apigenin (2) and sakuranetin (3) from this source. The isolated compounds were tested against Aspergillus flavus, Candida albicans, Candida glabrata, Fusarium solani, Microsporum canis and Trichoderma longibrachiatum. The results highlighted the antimicrobial activity of flavonoids 2 and 3, suggesting that this class of molecules may be responsible for the effect related to the traditional use. On the other hand, when the compounds and the extract were tested for their antiproliferative activity on a panel of 4 human cancer cell lines, the triterpene pistagremic acid (1) showed a higher potential, thus demonstrating a different bioactivity profile. Structure-based docking and molecular dynamics simulations were used to help the interpretation of experimental results. Taken together, the here reported findings pave the way for the rationalization of the use of P. chinensis extracts, highlighting the contributions of the different components of galls to the observed bioactivity.

The Bright Side of Psychedelics: Latest Advances and Challenges in Neuropharmacology.

The need to identify effective therapies for the treatment of psychiatric disorders is a particularly important issue in modern societies. In addition, difficulties in finding new drugs have led pharmacologists to review and re-evaluate some past molecules, including psychedelics. For several years there has been growing interest among psychotherapists in psilocybin or lysergic acid diethylamide for the treatment of obsessive-compulsive disorder, of depression, or of post-traumatic stress disorder, although results are not always clear and definitive. In fact, the mechanisms of action of psychedelics are not yet fully understood and some molecular aspects have yet to be well defined. Thus, this review aims to summarize the ethnobotanical uses of the best-known psychedelic plants and the pharmacological mechanisms of the main active ingredients they contain. Furthermore, an up-to-date overview of structural and computational studies performed to evaluate the affinity and binding modes to biologically relevant receptors of ibogaine, mescaline, N,N-dimethyltryptamine, psilocin, and lysergic acid diethylamide is presented. Finally, the most recent clinical studies evaluating the efficacy of psychedelic molecules in some psychiatric disorders are discussed and compared with drugs already used in therapy.

9,10-Bis[(4-(2-hydroxyethyl)piperazine-1-yl)prop2-yne-1-yl]anthracene: G-Quadruplex Selectivity and Anticancer Activity.

G-Quadruplexes (G4s) are appealing targets for anticancer therapy because of their location in the genome and their role in regulating physiological and pathological processes. In this article, we report the characterization of the molecular interaction and selectivity of OAF89, a 9,10-disubstituted G4-binding anthracene derivative, with different DNA sequences. Advanced analytical methods, including mass spectrometry and nuclear magnetic resonance, were used to conduct the investigation, together with the use of in silico docking and molecular dynamics. Eventually, the compound was tested in vitro to assess its bioactivity against lung cancer cell lines.

Dinaphthodiospyrol H: a natural α-glucosidase inhibibitor extracted from Diospyros kaki L.f.

The roots of Diospyro kaki L.f., known for their anti-inflammatory, antimicrobial and antidiabetic properties, are the source of dimeric naphthoquinones, including dinaphthodiospyrol H. α-Glucosidase is an enzyme involved in regulation of blood glucose levels and its inhibition helps in the control of the postprandial hyperglycaemia. In this study, an in vitro evaluation of dinaphthodiospyrol H was carried out and the compound inhibited α-glucosidase with an IC50 value of 57.38 ± 0.87 µg/mL, revealing a significant potential that supports the traditional application of D. kaki in the treatment of diabetes mellitus. Additionally, computational studies, including docking and molecular dynamics, were used to investigate ligand-target complex and showed that the compound targets the same site with which acarbose interacts. Overall, the findings provide new basis to translate the traditional use of D. kaki into modern medicinal chemistry.

Virtual Screening-Accelerated Discovery of a Phosphodiesterase 9 Inhibitor with Neuroprotective Effects in the Kainate Toxicity In Vitro Model.

In the central nervous system, some specific phosphodiesterase (PDE) isoforms modulate pathways involved in neuronal plasticity. Accumulating evidence suggests that PDE9 may be a promising therapeutic target for neurodegenerative diseases. In the current study, computational techniques were used to identify a nature-inspired PDE9 inhibitor bearing the scaffold of an isoflavone, starting from a database of synthetic small molecules using a ligand-based approach. Furthermore, docking studies supported by molecular dynamics investigations allowed us to evaluate the features of the ligand-target complex. In vitro assays confirmed the computational results, showing that the selected compound inhibits the enzyme in the nanomolar range. Additionally, we evaluated the expression of gene and protein levels of PDE9 in organotypic hippocampal slices, observing an increase following exposure to kainate (KA). Importantly, the PDE9 inhibitor reduced CA3 damage induced by KA in a dose-dependent manner in organotypic hippocampal slices. Taken together, these observations strongly support the potential of the identified nature-inspired PDE9 inhibitor and suggest that such a molecule could represent a promising lead compound to develop novel therapeutic tools against neurological diseases..