Structure Revision of Formyl Phloroglucinol Meroterpenoids: A Unified Approach Using NMR Fingerprinting and DFT NMR and ECD Analyses.

NMR fingerprints are valuable tools for analyzing complex natural product mixtures and identifying incorrectly assigned structures in the literature. Our diagnostic NMR fingerprints for formyl phloroglucinol meroterpenoids revealed discrepancies in the structures reported for eucalyprobusal C (1a) and eucalypcamal K (2a). NMR fingerprinting PCA analyses identified 1a as an oxepine-diformyl phloroglucinol and 2a as an oxepine 3-acyl-1-formyl phloroglucinol, contrary to their initial assignments as pyrano-diformyl and pyrano 3-acyl-1-formyl phloroglucinols, respectively. Extensive reinterpretation of their reported one- and two-dimensional NMR data, coupled with GIAO DFT-calculated 1H and 13C NMR chemical shift and DP4+ analyses, supported the unequivocal reassignment of eucalyprobusal C to 1b and eucalypcamal K to 2b. The absolute configurations of the revised oxepine-containing phloroglucinol meroterpenoids were confirmed via the reinterpretation of their reported ROESY and NOESY NMR data, along with comparative TDDFT-calculated and experimental ECD spectra.

Family Myrtaceae: The treasure hidden in the complex/diverse composition.

Myrtaceae is one of the most important plants families, being regarded as the eighth largest flowering plant family. It includes many genera of utmost ecological and economical importance distributed all over the world. This review aimed to report the latest studies on this family focusing on certain widely used plants including Eucalyptus sp., Eugenia sp. (Eugenia uniflora, Eugenia sulcata), Syzygium sp. (Syzygium aromaticum and Syzygium cumini), Psidium sp., Pimenta dioica, Myrtus sp. (Myrtus communis), Myrciaria sp. and Melaleuca alternifolia. The extraction of bioactive compounds has been evolving through the optimization of conventional methods and the use of emerging technologies. Supercritical CO2 was applied for essential oils and ultrasound for polyphenols leading to extracts and essential oils rich in bioactive compounds. Advances in the field of encapsulation and delivery systems showed promising results in the production of stable essential oils nanoemulsions and liposomes and the production of plant extracts in the form of nanoparticles. Moreover, a significant increase in the number of patents was noticed especially the application of Myrtaceae extracts in the pharrmacuetucal field. The applications of ceratin plants (Pimenta dioica, Melaleuca alternifolia, Syzygium aromaticum essential oils or Myrciaria cauliflora peel extract) in food area (either as a free or encapsulated form) also showed interesting results in limiting microbial spoilage of fresh meat and fish, slowing oxidative degradation in meat products, and inhibiting aflatoxin production in maize. Despite the massive literature on Myrtaceae plants, advances are still necessary to optimize the extraction with environmentally friendly technologies and carry out risk assessment studies should be accomplished to harness the full potential in food, industrial and pharmaceutical applications.

Oligomeric phloroglucinols with hAChE inhibitory and antibacterial activities from tropic Rhodomyrtus tomentosa.

Alzheimer's diseases (AD) and other infectious diseases caused by drug-resistance bacteria have posed a serious threat to human lives and global health. With the aim to search for human acetylcholinesterase (hAChE) inhibitors and antibacterial agents from medicinal plants, 16 phloroglucinol oligomers, including two new phloroglucinol monomers (1a and 1b), four new phloroglucinol dimers (3a, 3b, 4b, and 5a), six new phloroglucinol trimers (6a, 6b, 7a, 7b, 8a, and 8b), and two naturally occurring phloroglucinol monomers (2a and 2b), along with two known congeners (4a and 5b), were purified from the leaves of tropic Rhodomyrtus tomentosa. The structures and absolute configurations of these new isolates were unequivocally established by comprehensive analyses of their spectroscopic data (NMR and HRESIMS), ECD calculation, and single crystal X-ray diffraction. Structurally, 3a/3b shared a rare C-5' formyl group, whereas 6a/6b possessed a unique C-7' aromatic ring. In addition, 7a/7b and 8a/8b were rare phloroglucinol trimers with a bis-furan and a C-6' hemiketal group. Pharmacologically, the mixture of 3a and 3b showed the most potent human acetylcholinesterase (hAChE) inhibitory activity with an IC50 value of 1.21 ± 0.16 µM. The molecular docking studies of 3a and 3b in the hAChE binding sites were performed, displaying good agreement with the in vitro inhibitory effects. In addition, the mixture of 3a and 3b displayed the most significant anti-MRSA (methicillin-resistant Staphylococcus aureus) with MIC and MBC values of both 0.50 µg/mL, and scanning electron microscope (SEM) studies revealed that they could destroy the biofilm structures of MRSA. The findings provide potential candidates for the further development of anti-AD and anti-bacterial agents.

Biomimetic Synthesis of an Antiviral Cinnamoylphloroglucinol Collection from Cleistocalyx operculatus: A Synthetic Strategy Based on Biogenetic Building Blocks.

A synthetic strategy based on biogenetic building blocks for the collective and divergent biomimetic synthesis of cleistoperlones A-F, a cinnamoylphloroglucinol collection discovered from Cleistocalyx operculatus, has been developed. These syntheses proceeded successfully in only six to seven steps starting from commercially available 1,3,5-benzenetriol and involving oxidative activation of stable biogenetic building blocks as a crucial step. Key features of the syntheses include a unique Michael addition/ketalization/1,6-addition/enol-keto tautomerism cascade reaction for the construction of the dihydropyrano[3,2-d]xanthene tetracyclic core of cleistoperlones A and B, and a rare inverse-electron-demand hetero-Diels-Alder cycloaddition for the establishment of benzopyran ring in cleistoperlones D-F. Moreover, cleistoperlone A exhibited significant antiviral activity against acyclovir-resistant strains of herpes simplex virus type 1 (HSV-1/Blue and HSV-1/153).

New dimeric phloroglucinol derivatives from Agrimonia pilosa and their hepatoprotective activities.

Five new dimeric phloroglucinol derivatives, agrimones A - E (1-5), were isolated from the whole plant of Agrimonia pilosa. Their structures including absolute configurations were determined by a series of spectroscopic data (UV, IR, HR-ESI-MS, 1D and 2D NMR), complemented with the comparison of the experimental and calculated ECD spectra, and gauge-independent atomic orbital (GIAO) NMR calculations. Notably, compounds 1 and 2 represent a highly oxidized 6/6/6 tricyclic ring skeleton based on the cis-fused paraquinone and chroman. Compounds 1a, 4, and 5 exhibited moderate hepatoprotective activities against APAP-induced HepG2 cell injury at 10 µM.

An Integrated LC-ESI-MSn and High Resolution LC-ESI-QTOF Approach for the Identification of Phloroglucinols from Nepalese Hypericum japonicum.

Phloroglucinols are characteristic constituents of Hypericumjaponicum that are claimed to exert several bioactivities, such as anti-inflammatory, anti-depressant and anti-viral ones. Phloroglucinols are unstable compounds and their synthesis is challenging; thus, isolation from natural sources is still one of the main strategies for obtaining these constituents in purified form. Assessing the presence of phloroglucinols in plant materials can be of interest for compound isolation, and LC-MS approaches afford sensitivity and specificity in this regard. In this work, we combined data from quadrupole-time of flight (QTOF) and ion trap (IT) mass spectrometers in order to assess the presence of the phloroglucinols characteristic of H. japonicum and to elucidate their MS fragmentation pathways. The identified compounds present similar structures bearing the 1,3,5-trihydroxybenzene core with different substitutions, which, in constituents at higher MW, is linked to 3',3'-dimethyl-6'-oxo-phlorisobutyrophenone by a methylene bridge. Differences in MS2 spectra of the considered phloroglucinols are useful for compound identification and differentiation, and to perform dereplication studies. Overall, the proposed approach could be useful for the analysis of phloroglucinols in H. japonicum and other plant species.

Phloroglucinol Derivatives from Dryopteris crassirhizoma as Potent Xanthine Oxidase Inhibitors.

Dryopteris crassirhizoma rhizomes are used as a traditional medicine in Asia. The EtOAc extract of these roots has shown potent xanthine oxidase (XO) inhibitory activity. However, the main phloroglucinols in D. crassirhizoma rhizomes have not been analyzed. Thus, we investigated the major constituents responsible for this effect. Bioassay-guided purification isolated four compounds: flavaspidic acid AP (1), flavaspidic acid AB (2), flavaspidic acid PB (3), and flavaspidic acid BB (4). Among these, 1 showed the most potent inhibitory activity with a half-maximal inhibitory concentration (IC50) value of 6.3 µM, similar to that of allopurinol (IC50 = 5.7 µM) and better than that of oxypurinol (IC50 = 43.1 µM), which are XO inhibitors. A comparative activity screen indicated that the acetyl group at C3 and C3' is crucial for XO inhibition. For example, 1 showed nearly 4-fold higher efficacy than 4 (IC50 = 20.9 µM). Representative inhibitors (1-4) in the rhizomes of D. crassirhizoma showed reversible and noncompetitive inhibition toward XO. Furthermore, the potent inhibitors were shown to be present in high quantities in the rhizomes by a UPLC-QTOF-MS analysis. Therefore, the rhizomes of D. crassirhizoma could be used to develop nutraceuticals and medicines for the treatment of gout.

Volatiles from the Mandibular Gland Reservoir Content of Colobopsis explodens Laciny and Zettel, 2018, Worker Ants (Hymenoptera: Formicidae).

Forty-five volatile organic compounds (VOCs) were identified or annotated in the mandibular gland reservoir content (MGRC) of the Southeast Asian ant Colobopsis explodens Laciny and Zettel, 2018 (Hymenoptera: Formicidae), using headspace solid-phase microextraction (HS-SPME) coupled to gas chromatography mass spectrometry (GC-MS) and liquid extraction combined with GC-MS. In extension of previous reports on VOCs of C. explodens, members of different compound classes, such as alkanes, aliphatic and aromatic carboxylic acids, and phenolics, were detected. The ketone 2-heptanone and the biochemically related phenolics benzene-1,3,5-triol (phloroglucinol, PG), 1-(2,4,6-trihydroxyphenyl)ethanone (monoacetylphloroglucinol, MAPG), 5,7-dihydroxy-2-methylchromen-4-one (noreugenin), and 1-(3-Acetyl-2,4,6-trihydroxyphenyl)ethanone (2,4-diacetylphloroglucinol, DAPG) dominated the GC-MS chromatograms. The identities of the main phenolics MAPG and noreugenin were further verified by liquid chromatography-high resolution-tandem mass spectrometry (LC-HRMS/MS). A comparative study of MGRC samples originating from three distinct field expeditions revealed differences in the VOC profiles, but the presence and relative abundances of the dominating constituents were largely consistent in all samples. Our study considerably extends the knowledge about the number and type of VOCs occurring in the MGRC of C. explodens. Based on the type of the detected compounds, we propose that the likely irritant and antibiotic phenolic constituents play a role in defense against arthropod opponents or in protection against microbial pathogens.

Phenotyping the genus Hypericum by secondary metabolite profiling: emodin vs. skyrin, two possible key intermediates in hypericin biosynthesis.

A wide range of compounds that occur in the genus Hypericum are listed as effective drugs of natural origin. The main biological activities of several Hypericum representatives are due to the presence of naphthodianthrones, phloroglucinols, and other diverse groups of secondary metabolites that synergistically contribute to their therapeutic effects. The regulation of biosynthesis of hypericin as the key bioactive naphthodianthrone remains uncertain. Here, we present liquid chromatography mass spectrometry-based phenotyping of 17 Hypericum species, the results of which suggest an important role for skyrin and its derivatives in the polyketide pathway that leads to hypericin formation. Moreover, we report for the first time the presence of new metabolites in the genus Hypericum that are related to classes of anthraquinones, their derivatives, and phloroglucinols. As skyrin and other species of anthraquinones are rarely found in higher plants but frequently occur in fungal microorganisms, the obtained results suggest that further research on the synthesis pathways of hypericin and the role of anthraquinone derivatives in plant metabolism should be carried out. The fact that these compounds are commonly synthesized in endophytic fungi and perhaps there is some similarity in the metabolic pathways between these organisms should also be investigated.

Arbuscular mycorrhizal fungi altered the hypericin, pseudohypericin, and hyperforin content in flowers of Hypericum perforatum grown under contrasting P availability in a highly organic substrate.

St. John's Wort (Hypericum perforatum) is a perennial herb able to produce water-soluble active ingredients (a.i.), mostly in flowers, with a wide range of medicinal and biotechnological uses. However, information about the ability of arbuscular mycorrhizal fungi (AMF) to affect its biomass accumulation, flower production, and concentration of a.i. under contrasting nutrient availability is still scarce. In the present experiment, we evaluated the role of AMF on growth, flower production, and concentration of bioactive secondary metabolites (hypericin, pseudohypericin, and hyperforin) of H. perforatum under contrasting P availability. AMF stimulated the production of aboveground biomass under low P conditions and increased the production of root biomass. AMF almost halved the number of flowers per plant by means of a reduction of the number of flower-bearing stems per plant under high P availability and through a lower number of flowers per stem in the low-P treatment. Flower hyperforin concentration was 17.5% lower in mycorrhizal than in non-mycorrhizal plants. On the contrary, pseudohypericin and hypericin concentrations increased by 166.8 and 279.2%, respectively, with AMF under low P availability, whereas no effect of AMF was found under high P availability. These results have implications for modulating the secondary metabolite production of H. perforatum. However, further studies are needed to evaluate the competition for photosynthates between AMF and flowers at different nutrient availabilities for both plant and AM fungus.

Anti-Influenza Virus (H5N1) Activity Screening on the Phloroglucinols from Rhizomes of Dryopteris crassirhizoma.

For screening the active phloroglucinols on influenza virus (H5N1) from Dryopteris crassirhizoma NaKai, a database was established including twenty-three phloroglucinols that had been isolated from Dryopteris crassirhizoma. Their inhibitory effect on the neuraminidase (NA) of influenza virus H5N1 was screened by molecular docking. As a result, three candidates were selected. The rhizomes of D. crassirhizoma were subjected to isolation and purification processes to obtain the inhibitor candidates. Thirteen phloroglucinols were obtained, including three selected candidates and two new phloroglucinols. The five phloroglucinols were investigated for their inhibitory activity on NA in vitro. The results showed that dryocrassin ABBA and filixic acid ABA exhibited inhibitory effects on NA with IC50 as 18.59 ± 4.53 and 29.57 ± 2.48 µM, respectively, and the other three phloroglucinols showed moderate inhibitory activity. Moreover, the anti-influenza virus (H5N1) activity and cytotoxicity of dryocrassin ABBA and filixic acid ABA were tested on Madin-Darby canine kidney (MDCK) cells with the cell counting kit-8 (CCK8) method. The results confirmed that dryocrassin ABBA exhibited an inhibitory activity with low cytotoxicity (TC50 > 400 µM) against influenza virus (H5N1) which will have to be investigated in further detail. In conclusion, phloroglucinols from D. crassirhizoma were shown to have anti-influenza virus activity, and especially dryocrassin ABBA, one of the phloroglucinols, may have the potential to control influenza virus (H5N1) infection.

Secondary metabolites of seven Hypericum species growing in Turkey.

Context The genus Hypericum (Hypericaceae) has attracted remarkable scientific interest as its members have yielded many bioactive compounds. Objective The current study presents investigations on the accumulation of hypericin, pseudohypericin, hyperforin, adhyperforin, chlorogenic acid, neochlorogenic acid, caffeic acid, 2,4-dihydroxybenzoic acid, 13,118-biapigenin, hyperoside, isoquercitrin, quercitrin, quercetin, avicularin, rutin, (+)-catechin and (-)-epicatechin in seven Hypericum (Hypericaceae) species growing wild in Turkey, namely, H. aviculariifolium Jaup. and Spach subsp. aviculariifolium (Freyn and Bornm.) Robson var. albiflorum (endemic), H. bithynicum Boiss., H. calycinum L., H. cardiophyllum Boiss., H. elongatum L. subsp. microcalycinum (Boiss. and Heldr.) Robson, H. hirsutum L. and H. xylosteifolium (Spach) N. Robson. Materials and methods The plant materials were collected at flowering period and dissected in different tissues. Air-dried plant material including stems, leaves and flowers was mechanically powdered with a laboratory mill and samples (0.1 g) were extracted in 10 mL of 100% methanol by ultrasonication at 40 °C for 30 min for HPLC-PDA analyses. Results Accumulation levels of the investigated compounds varied greatly depending on species and plant part. Discussion For the first time, the detailed chemical profiles of corresponding Turkish Hypericum species were reported and the results were discussed from a phytochemical point of view. Conclusions The present data have importance in evaluation of plant resources of Hypericum genus in selecting the new potential sources of bioactive compounds.

Acylphloroglucinol Derivatives from the South African Helichrysum niveum and Their Biological Activities.

Phytochemical investigation of aerial parts of Helichrysum niveum (H. niveum) using different chromatographic methods including semi-preparative HPLC afforded three new (1-3) and six known (4-10) acylphloroglucinols alongside a known dialcohol triterpene (11). The structures of the isolated compounds were characterized accordingly as 1-benzoyl-3 (3-methylbut-2-enylacetate)-phloroglucinol (helinivene A, 1), 1-benzoyl-3 (2S-hydroxyl-3-methylbut-3-enyl)-phloroglucinol (helinivene B, 2), 8-(2-methylpropanone)-3S,5,7-trihydroxyl-2,2-dimethoxychromane (helinivene C, 3), 1-(2-methylbutanone)-4-O-prenyl-phloroglucinol (4), 1-(2-methylpropanone)-4-O-prennyl-phloroglucinol (5), 1-(butanone)-3-prenyl-phloroglucinol (6), 1-(2-methylbutanone)-3-prenyl-phloroglucinol (7), 1-butanone-3-(3-methylbut-2-enylacetate)-phloroglucinol (8), 1-(2-methylpropanone)-3-prenylphloroglucinol (9), caespitate (10), and 3ß-24-dihydroxyterexer-14-ene (11). Excellent total antioxidant capacities were demonstrated by helinivenes A and B (1 and 2) when measured as oxygen radicals absorbance capacity (ORAC), ferric-ion reducing antioxidant power (FRAP), trolox equivalent absorbance capacity (TEAC) and including the inhibition of Fe(2+)-induced lipid peroxidation (IC50 = 5.12 ± 0.90; 3.55 ± 1.92) µg/mL, while anti-tyrosinase activity at IC50 = 35.63 ± 4.67 and 26.72 ± 5.05 µg/mL were also observed for 1 and 2, respectively. This is the first chemical and in vitro biological study on H. niveum. These findings underpin new perspectives for the exploitation of these natural phenolic compounds in applications such as in the natural cosmeceutical and pharmaceutical sectors.

Acetylcholinesterase inhibitory phloroglucinols from tropic Rhodomyrtus tomentosa.

Four previously undescribed phloroglucinols, including three pairs of enantiomers, (±)-rhodotomentodimer F, (±)-rhodotomentodimer G, and (±)-rhodotomentomonomer E, and one phloroglucinol-sesquiterpene meroterpenoid, rhodotomentodione E, together with one previously reported congener, (±)-rhodomyrtosone A, were obtained from the leaves of Rhodomyrtus tomentosa. The structures including absolute configurations of previously undescribed isolates were elucidated by extensive spectroscopic analysis (HRESIMS and NMR), ECD calculations, and single-crystal X-ray diffraction. (±)-Rhodotomentodimer F is a rare phloroglucinol derivative conjugated by a ß-triketone moiety and an unprecedented resorcinol unit via the formation of a rare bis-furan ring system, whereas (±)-rhodotomentomonomer E shares a rearranged pentacyclic scaffold. Pharmacologically, (±)-rhodotomentomonomer E showed the strongest human acetylcholinesterase (hAChE) inhibitory effect with an IC50 value of 1.04 ± 0.05 µM. Molecular formula studies revealed that hydrogen bonds formed between hAChE residues Glu202, Ser203, Ala204, Gly121, Gly122, Tyr337, and His447 and (±)-rhodotomentomonomer E played crucial roles in its observed activity. These findings indicated that the leaves of Rhodomyrtus tomentosa can supply a rich source of hAChE inhibitors. These inhibitors might potentially be utilized in the therapeutic strategy for Alzheimer's disease, offering promising candidates for further research and development.

Phytochemical profiling and neuroprotective activity of Callistemon subulatus leaves against cyclophosphamide-induced chemobrain.

Cyclophosphamide (CPA) is a chemotherapeutic drug used for various types of cancers. However, patients receiving CPA for long periods suffer cognitive impairment associated with difficulties in learning, decreased concentration, and impaired memory. Chemotherapy-induced cognitive impairment, known as chemobrain, has been attributed to enhanced oxidative stress and inflammatory response. The current study aimed to identify the phytoconstituents of Callistemon subulatus extract (CSE) using HPLC-ESI/MS-MS analysis and evaluate its neuroprotective activity against CPA-induced chemobrain in rats. Fourteen compounds were identified following HPLC analysis including, five phlorglucinols, four flavonol glycosides, a triterpene, and a phenolic acid. Forty rats were divided into five groups treated for ten days as follows; group I (control group), group II received CPA (200 mg/kg, i.p.) on the 7th day, groups III and IV received CSE (200 and 400 mg/kg respectively, orally) for ten days and CPA (200 mg/kg, i.p.) on the 7th day, and group V received only CSE (400 mg/kg, orally) for ten days. The administration of CSE effectively ameliorated the deleterious effects of CPA on spatial and short-term memories, as evidenced by behavioral tests, Y-maze and passive avoidance. Such findings were further confirmed by histological examination. In addition, CSE counteracted the effect of CPA on hippocampal acetylcholinesterase (AChE) activity enhancing the level of acetylcholine. Owing to the CSE antioxidant properties, it hindered the CPA-induced redox imbalance, which is represented by decreased catalase and reduced glutathione levels, as well as enhanced lipid peroxidation. Therefore, CSE may be a promising natural candidate for protection against CPA-induced chemobrain in cancer patients.

Cytotoxic Isopentenyl Phloroglucinol Compounds from Garcinia xanthochymus Using LC-MS-Based Metabolomics.

Many unique chemical metabolites with significant antitumor activities have been isolated from Garcinia species and have become a leading hotspot of antitumor research in recent years. The aim of this study was to identify bioactive compounds from different plant parts (leaf, branch, stem bark, fruit, and seed) of G. xanthochymus through combining LC-MS-based metabolomics with cytotoxicity assays. As a result, 70% methanol seed extract exerted significant cytotoxic effects on five human cancer cell types (HL-60, A549, SMMC-7721, MDA-MB-231, and SW480). LC-MS-based metabolomics analysis was used, including principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA), in order to identify 12 potential markers from seed extract that may relate to bioactivity. LC-MS guidance isolated the markers to obtain three compounds and identified new isopentenyl phloroglucinols (1-3, named garxanthochin A-C), using spectroscopic methods. Among them, garxanthochin B (2) demonstrated moderate inhibitory activities against five human cancer cell types, with IC50 values of 14.71~24.43 µM. These findings indicate that G. xanthochymus seed has significant cytotoxic activity against cancer cells and garxanthochin B has potential applications in the development of antitumor-led natural compounds.

Metabolomics characterizes early metabolic changes and markers of tolerant Eucalyptus ssp. clones against drought stress.

EUCALYPTUS: L'Hér. (Myrtaceae) is one of the economically most important and widely cultivated trees for wood crop purposes worldwide. Climatic changes together with the constant need to expand plantations to areas that do not always provide optimal conditions for plant growth highlight the need to assess the impact of abiotic stresses on eucalypt trees. We aimed to unveil the drought effect on the leaf metabolome of commercial clones with differential phenotypic response to this stress. For this, seedlings of 13 clones were grown at well-watered (WW) and water-deficit (WD) conditions and their leaf extracts were subjected to comparative analysis using ultra-high performance liquid chromatography coupled to mass spectrometry (UPLC-MS) and nuclear magnetic resonance spectroscopy (NMR). UPLC-MS and NMR analyses led to the annotation of over 100 molecular features of classes such as cyclitols, phenolics, flavonoids, formylated phloroglucinol compounds (FPCs) and fatty acids. Multivariate data analysis was employed for specimens' classifications and markers identification from both platforms. The results obtained in this work allowed us to classify clones differing in drought tolerance. Classification models were validated using an extra subset of samples. Tolerant plants exposed to water deficit accumulated arginine, gallic acid derivatives, caffeic acid and tannins at higher levels. In contrast, stressed drought-sensitive clones were characterised by a significant reduction in glucose, inositol and shikimic acid levels. These changes in contrasting drought response eucalypt pave ways for differential outcomes of tolerant and susceptible phenotypes. Under optimal growth conditions, all clones were rich in FPCs. These results can be used for early screening of tolerant clones and to improve our understanding of the role of these biomarkers in Eucalyptus tolerance to drought stress.

Monoterpenoid acylphloroglucinols from Hypericum hengshanense W. T. Wang with antiproliferative activities.

Hypericum species (Hypericaceae) are a group of important plants with medicinal, edible, and ornamental values. A phytochemical study on the whole plants of H. hengshanense W. T. Wang, a species endemic to China, led to the isolation and elucidation of 25 monoterpenoid acylphloroglucinols (MAPs). Among them, 10 are undescribed compounds, namely hyphengshanols A-D, (+)-empetrilatinol A, (-)-empetrilatinol B, (-)-hyperjovinol A, (9S,2'S)-dauphinol F, and (8R,2'S)-empetrikathiforin. In addition, the absolute configurations of other six compounds were firstly determined in the current study. The structures were established by ultraviolet (UV), high resolution electrospray ionization mass spectrum (HR-ESI-MS), and nuclear magnetic resonance spectroscopy (NMR) data. The absolute configurations were determined by experimental and calculated electronic circular dichroism (ECD) data analyses. Cytotoxicity assays on five human cell lines HL-60, A549, SMMC-7721, MDA-MB-231, and SW480 revealed that 16 compounds exhibited broad-spectrum antiproliferative activities with IC50 ranging from 7.54 to 45.70 µM.

Corrigendum: Identification and metabolomic characterization of potent anti-MRSA phloroglucinol derivatives from Dryopteris crassi rhizoma Nakai (Polypodiaceae).

[This corrects the article DOI: 10.3389/fphar.2022.961087.].

Eucalyptals D and E, new cytotoxic phloroglucinols from the fruits of Eucalyptus globulus and assignment of absolute configuration.

Two new phloroglucinols, named eucalyptals D (1) and E (2), along with a related known compound (euglobal-In-3, 3) were isolated from the fruits of Eucalyptus globulus. Their structures were established on the basis of extensive spectroscopic studies, revealing that they share a common 3,5-diformyl-isopentyl phloroglucinol unit, but each is instead coupled to a different sesquiterpenoid skeleton (aromadendrene in 1, cadinene in 2, and a spirosesquiterpene in 3). Compound 1 possessed an unusual seven-membered D ring with an ether bridge between C-2 of the aromadendrene moiety and C-2' of the aromatic unit. The absolute configuration of the isolates was defined by the comparison of experimental and calculated electronic circular dichroism (ECD) spectra. Compounds 1-3 exhibited significant in vitro cytotoxicities against a few human cancer cell lines (Huh-7, Jurkat, BGC-823, and KE-97) using the CellTiter-Glo™ luminescent cell viability assay method.