Biomimetic synthesis of rare cannabigerol-type cannabinoids and evaluation of their cytotoxic effect on human glioblastoma cell lines.

Although Cannabis sativa L. is well known for being prolific in phytocannabinoids, their biosynthetic modular mechanism is ruled by a main enzyme: the geranyltransferase able to pursue the C-isoprenylation of olivetolic acid with the geranyldiphosphate. However, the existence of more than 160 meroterpenoids can be partially explained by a side degree of promiscuity of the geranyltransferase itself, able to recognise different substrate than the ordinary ones.

Untargeted metabolomics profiling of Morus alba twigs extract and antibacterial activity of pure metabolites.

Plant natural products offer promise in combating multi-drug resistance by acting as antibacterial agents through various mechanisms. A metabolomic-guided phytochemical investigation, based on a LC-HRMS/MS and Molecular Networking combined approach, was carried out on an extract of M. alba L.

Marine Pharmacology in 2019-2021: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis and Antiviral Activities; Affecting the Immune and Nervous Systems, and Other Miscellaneous Mechanisms of Action.

The current 2019-2021 marine pharmacology literature review provides a continuation of previous reviews covering the period 1998 to 2018. marine pharmacology research during 2019-2021 was published by researchers in 42 countries and contributed novel mechanism-of-action pharmacology for 171 structurally characterized marine compounds. The peer-reviewed marine natural product pharmacology literature reported antibacterial, antifungal, antiprotozoal, antituberculosis, and antiviral mechanism-of-action studies for 49 compounds, 87 compounds with antidiabetic and anti-inflammatory activities that also affected the immune and nervous system, while another group of 51 compounds demonstrated novel miscellaneous mechanisms of action, which upon further investigation, may contribute to several pharmacological classes.

Metabolites from Aerial Parts of as Modulators of Targets Related to Metabolic Syndrome.

A detailed phytochemical investigation has been carried out on the aerial parts of leading to the isolation of 29 pure compounds, mainly belonging to the amorfrutin and polyphenol classes. Among them, the new amorfrutin N () and exiguaflavone L () were isolated and their structures elucidated by means of HR-ESIMS and NMR. All the isolated compounds were investigated for modulation of mitochondrial activity and stimulation of glucose uptake via GLUT transporters, two metabolic processes involved in intracellular glucose homeostasis, which, therefore, correlate with the incidence of metabolic syndrome.

Glucose Uptake-Stimulating Metabolites from Aerial Parts of .

A comprehensive phytochemical investigation of aerial parts obtained from L. led to the isolation of 14 terpenoids (-) and nine polyphenols (-). The sesquiterpenoid group (-) included three structural families, namely, elemanolides (-), eudesmanolides ( and ), and germacranolides (-) with four unreported secondary metabolites (-), whose structure has been determined by extensive spectroscopic analysis, including 1D/2D NMR, HR-MS, and chemical conversion.

Phytochemical Characterization and TRPA1/TRPM8 Modulation Profile of the Cannabigerol-Rich L. Chemotype IV.

The first detailed phytochemical analysis of the cannabigerol (CBG)-rich chemotype IV of L. resulted in the isolation of the expected cannabigerolic acid/cannabigerol (CBGA/CBG) and cannabidiolic acid/cannabidiol (CBDA/CBD) and of nine new phytocannabinoids (-), which were fully characterized by HR-ESIMS and 1D and 2D NMR. These included mono- or dihydroxylated CBGA/CBG analogues, a congener with a truncated side chain (), cyclocannabigerol B (), and the CBD derivatives named cannabifuranols ( and ).

The Eleutherococcus senticosus fruits' intractum affects changes in the transepithelial electric potential in the distal section of the rabbit's large intestine and inhibits hyaluronidase.

Ethnopharmacological Relevance: Eleutherococcus senticosus (Rupr. et Maxim.) Maxim.

Antibacterial Metabolites Produced by an Endemic Plant of Lampedusa Island.

Lampedusa, the largest island of the Pelagie archipelago, Sicily, Italy, has proven to be a rich source of plants and shrubs used in folk medicine. These plants, often native to the island, have been very poorly investigated for their phytochemical composition and biological potential to be translated into pharmacological applications. To start achieving this purpose, a specimen of , a plant native to Lampedusa, was investigated for the first time.

Isochlorogenic Acid Glucosides from the Arabian Medicinal Plant and Their Antimicrobial Activities.

A phytochemical investigation of the stems of the Arabian plant afforded three new isochlorogenic acid derivatives, namely isochlorogenic acid A-3'---glucopyranoside (), isochlorogenic acid A-3'---glucopyranoside methyl ester (), and isochlorogenic acid C-3'---glucopyranoside (), obtained along with thirteen known secondary metabolites belonging to distinct structural classes. The structures of the new metabolites were elucidated by modern spectroscopic techniues based on high-resolution mass spectrometry (HR-ESIMS) and 1D/2D nuclear magnetic resonance (NMR). All isolated compounds were tested for their potential antimicrobial activity against four different bacterial strains (, , , and ), in addition to a fungal strain (), The results were expressed as the diameter of the clear zone (in millimetres) around each well.

Novel Skeletal Rearrangements of the Tigliane Diterpenoid Core.

To investigate the role of the secondary 5-hydroxy group in the activity of the anticancer drug tigilanol tiglate () (Stelfonta), oxidation of this epoxytigliane diterpenoid from the Australian rainforest plant was attempted. Eventually, 5-dehydrotigilanol tiglate () proved too unstable to be characterized in terms of biological activity and, therefore, was not a suitable tool compound for bioactivity studies. On the other hand, a series of remarkable skeletal rearrangements associated with the presence of a 5-keto group were discovered during its synthesis, including a dismutative ring expansion of ring A and a mechanistically unprecedented dyotropic substituent swap around the C-4/C-10 bond.

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.

Hydroxylated cyclopamine analogues from Veratrum californicum and their hedgehog pathway inhibiting activity.

Cyclopamine (1), the teratogenic steroidal alkaloid isolated from corn lily (Veratrum californicum), has recently gained renewed interest due to its anticancer potential, that has been translated into the FDA approval of three Hedgehog (Hh) pathway inhibiting antitumor drugs. A chemical analysis of mother liquors obtained from crystallization of cyclopamine, extracted from roots and rhizomes of V. californicum, resulted in the isolation of two unprecedented cyclopamine analogues, 18-hydroxycyclopamine (2) and 24R-hydroxycyclopamine (3), the first compounds of this class to show modifications on rings D-F.

Phytochemical profile and anti-inflammatory activity of a commercially available Rhodiola rosea root extract.

Rhodiola rosea roots and rhizomes hold an important place in the folk medicines of Russia, Scandinavia, Mongolia, and China as a health supplement for stimulating the nervous system, enhancing physical and mental performances, and nowadays they constitute the active ingredient in many popular commercial preparations sold worldwide as food additives, pharmaceutical remedies, and drinks. This study was aimed at providing a detailed phytochemical characterization of the Rhodiola 5%, a commercially available extract of R. rosea roots, and resulted in the characterization of 18 secondary metabolites, including 13 polyphenols and 6 terpenoids, and in the discovery of the new rhodiosidin (5), the first R.

Penicillactonin and preaustinoid C, lactone-containing metabolites from a hot spring sediment Penicillium sp.

Phytochemical investigation of Penicillium sp. RO-11 strain, collected from the sediments of a hydrothermal spring located in the southwestern area of Saudi Arabia, afforded, along with previously isolated compounds, the undescribed polyketides penicillactonin (1), penipyranicin D (4) and isopyrenulin B (5) and the undescribed meroterpenoid preaustinoid C (7). The structures of these compounds were elucidated based on data from mass spectrometry, 1D and 2D NMR, and comparison between experimental and calculated ECD spectra.

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.

Cryptic Epoxytiglianes from the Kernels of the Blushwood Tree ().

The kernels of the Australian blushwood tree () are the source of the veterinary anticancer drug tigilanol tiglate (, Stelfonta) and contain a concentration of phorboids significantly higher than croton oil, the only abundant source of these compounds previously known. The oily matrix of the blushwood kernels is composed of free fatty acids and not by glycerides as found in croton oil. By active partitioning, it was therefore possible to recover and characterize for the first time a cryptic tigliane fraction, that is, the diterpenoid fraction that, because of its lipophilicity, could not be obtained by solvent partition of crude extracts.

Marine pharmacology in 2018: Marine compounds with antibacterial, antidiabetic, antifungal, anti-inflammatory, antiprotozoal, antituberculosis and antiviral activities; affecting the immune and nervous systems, and other miscellaneous mechanisms of action.

The 2018 marine pharmacology literature review represents a continuation of the previous 11 reviews of a series initiated in 1998. Preclinical marine pharmacology research during 2018 was performed by investigators in 44 countries and contributed novel pharmacology for 195 marine compounds. The peer-reviewed marine natural products pharmacology literature reported antibacterial, antifungal, antiprotozoal, antituberculosis, and antiviral activities for 53 compounds, 73 compounds which presented antidiabetic and anti-inflammatory activities as well as affecting the immune and nervous system, while in contrast 69 compounds were reported to show miscellaneous mechanisms of action which may contribute upon further investigation to several pharmacological classes.

Guaiane-rich phytochemical profile of Centaurea kotschyi subsp. persica (Boiss.) Wagenitz and identification of hypoglycaemic metabolites.

Phytochemical investigation of the aerial parts obtained from the Turkish plant Centaurea kotschyi subsp. persica led to the isolation of nine sesquiterpene lactones belonging to the guaiane class, including the undescribed kotschyols A and B, a monoterpene lactone (daphnauranin E), four known lignans (matairesinol, matairesinoside, arctiin and arctigenin) and an undescribed dihydrobenzofuran neolignan (4-O-glucosylcrataegifin A). The structures of these compounds were defined by spectroscopic analysis, including ECD and 1D/2D NMR, and chemical conversion.

Euphocactoside, a New Megastigmane Glycoside from Growing in Saudi Arabia.

A phytochemical investigation of the aerial parts of Ehrenb. ex Boiss. revealed a new megastigmane, euphocactoside (), along with eleven known metabolites.

A Nrf-2 Stimulatory Hydroxylated Cannabidiol Derivative from Hemp ().

A phytochemical analysis of mother liquors obtained from crystallization of CBD from hemp (), guided by LC-MS/MS and molecular networking profiling and completed by isolation and NMR-based characterization of constituents, resulted in the identification of 13 phytocannabinoids. Among them, anhydrocannabimovone (), isolated for the first time as a natural product, and three new hydroxylated CBD analogues (1,2-dihydroxycannabidiol, , 3,4-dehydro-1,2-dihydroxycannabidiol, , and hexocannabitriol, ) were obtained. Hexocannabitriol () potently modulated, in a ROS-independent way, the Nrf2 pathway, outperforming all other cannabinoids obtained in this study and qualifying as a potential new chemopreventive chemotype against cancer and other degenerative diseases.

Phytochemical profile of Centevita®, a Centella asiatica leaves extract, and isolation of a new oleanane-type saponin.

Centella asiatica is a popular medicinal plant and several phytotherapic products in the market include its extracts as active constituents. A LC-MS guided phytochemical investigation on the commercial C. asiatica leaves extract named Centevita® allowed characterization and quantification of 24 secondary metabolites including 10 polyphenols and 14 ursane- or oleanane-type triterpenoids in the sapogenin or saponin form.

Cynarin blocks Ebola virus replication by counteracting VP35 inhibition of interferon-beta production.

Ebola virus (EBOV) is one of the deadliest infective agents whose lethality is linked to the ability to efficiently bypass the host's innate antiviral response. EBOV multifunctional protein VP35 plays a major role in viral replication both as polymerase cofactor and interferon (IFN) antagonist. By hiding the non-self 5'-ppp dsRNA from the cellular receptor RIG-I, VP35 prevents its activation and inhibits IFN-β production.

Total Synthesis of the Natural Chalcone Lophirone E, Synthetic Studies toward Benzofuran and Indole-Based Analogues, and Investigation of Anti-Leishmanial Activity.

The potential of natural and synthetic chalcones as therapeutic leads against different pathological conditions has been investigated for several years, and this class of compounds emerged as a privileged chemotype due to its interesting anti-inflammatory, antimicrobial, antiviral, and anticancer properties. The objective of our study was to contribute to the investigation of this class of natural products as anti-leishmanial agents. We aimed at investigating the structure-activity relationships of the natural chalcone lophirone E, characterized by the presence of benzofuran B-ring, and analogues on anti-leishmania activity.

Asporychalasin, a bioactive cytochalasan with an unprecedented 6/6/11 skeleton from the Red Sea sediment Aspergillus oryzae.

The cytochalasan asporychalasin (1) was obtained from the marine fungus Aspergillus oryzae, isolated from the Red Sea sediments collected off Jeddah, Saudi Arabia. The chemical structure of 1 was elucidated by extensive spectroscopic analysis and quantum-mechanical calculations of C NMR resonances and ECD to possess an unprecedented 6/6/11-fused tricyclic skeleton, including an isoquinolindione ring in place of the typical isoindolone. Asporychalasin exhibited moderate antiproliferative activity against three human cancer cell lines, lung carcinoma (A549), liver carcinoma (HepG2), and breast carcinoma (MCF7), and no toxicity on zebrafish embryos.