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Fifteen undescribed phenylpropanoyl phloroglucinol derivatives featuring modified isoprenyl and/or geranyl units (1-15), in conjunction with thirteen known analogues (16-28), were obtained from the glandular hairs of the fruit of Mallotus philippensis. Meanwhile, fourteen pairs of new enantiomers [(±)-1-9, (±)-11-15] were further resolved by chiral purification. Their structures were determined by comprehensive spectroscopic analyses, single-crystal X-ray diffraction experiments and quantum chemical calculations. Bioactivity evaluation showed that compound 17 exhibited significant anti-bacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) with MIC of 6 μg/mL, while compounds 3, 4, 8 and 18 displayed moderate effects with MIC of 24, 12, 24, and 12 μg/mL, respectively. The KEGG enrichment analysis of 17 revealed that the phosphotransferase system (PTS) pathway was significantly enriched. In addition, compound 17 was found to affect the amino acids biosynthesis and amino acids/carbohydrate metabolism, and the qRT-PCR verified the accuracy of the transcriptome analysis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Garciyunnanol A (1), an unprecedented 1,2-seco-bicyclic polyprenylated acylphloroglucinol (BPAP) possessing a unique 6/6/6 tricyclic core, was characterized from Garcinia yunnanensis together with 16 BPAPs, including eight new compounds (garciyunnanols B-I, 2-9). Biogenetically, the bicyclo[3.3.1]nonane-2,4,9-trione moiety of 12 reconstructed the bicyclic δ-lactone core of 2 through Norrish type Ⅰ cleavage and cyclization, followed by a cyclization of two side chains to form an intriguing 6/6/6 tricyclic core of 1. Their structures were elucidated through analysis of spectroscopic data, calculation and comparison of ECD spectra. Bioactivity evaluation manifested that compounds 1, 2, 5, 6 and 14 demonstrated superior inhibition of NO production compared to the positive control dexamethasone. Notably, compound 5 exhibited a dose-dependent inhibitory effect on NO production, with an IC 50 value of 0.25 ± 0.87 µM. Furthermore, experiments involving ELISA, Western blotting, and immunofluorescence staining revealed that 5 effectively reduced the secretion of interleukin-1β in LPS plus nigericin-stimulated THP-1 macrophages by inhibiting the activation of the NLRP3 inflammasome., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

The phytochemical investigation on the pericarps of Garcinia multiflora resulted in the isolation of 12 previously undescribed polycyclic polyprenylated acylphloroglucinols (PPAPs, 1-12) with a variety of skeletons. Their structures were determined by comprehensive spectroscopic analyses, ECD calculations, and single-crystal X-ray diffraction. Compounds 6-9 possess a rare bicyclo[4.3.1]decane skeleton. Additionally, the anti-tumor activity of the 12 isolates was evaluated. The results indicated that compounds 5, 9, and 12 exhibited significant cytotoxicity in a wide range of cancer cell lines, including the human breast cancer MDA-MB-231 cells, human lung cancer A549 cells, human colon cancer SW480 cells and human ovarian cancer HEY cells. Further studies indicated that compound 5 induced cell cycle arrest and apoptosis, to inhibit the growth of MDA-MB-231 cells. Taken together, these findings expand the chemical diversity of PPAPs and further demonstrate the potential of PPAPs as candidates for cancer treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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 β-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 IC 50 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Six new polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperidiones A-F (1-6), were obtained from Hypericum perforatum L. Their structures were characterized via extensive spectroscopic analyses, the circular dichroism data of the in situ formed [Mo 2 (OCOCH 3 ) 4 ] complexes, the nuclear magnetic resonance calculation with DP4 + probability analysis, and the calculated electronic circular dichroism (ECD) spectra. Compounds 1-6 are bicyclic polyprenylated acylphloroglucinols with a major bicyclo[3.3.1]nonane-2,4,9-trione skeleton. Notably, compound 1 is a rare PPAP with a hydroperoxy group, and a plausible biosynthetic pathway for 1 was proposed. Compounds 4 and 6 exhibited significant neuroprotective effects under 10 μM against corticosterone (CORT)-injured SH-SY5Y cells. Furthermore, compound 4 demonstrated a noteworthy antidepressant effect at the dose of 5 mg/kg in the tail suspension test (TST) of mice, which was equivalent to 5 mg/kg of fluoxetine. And it potentially exerted an antidepressant effect through the hypothalamic-pituitary-adrenal (HPA) axis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Garciyunnanones A-R (1-18), eighteen undescribed caged polycyclic polyprenylated acylphloroglucinols, two undescribed biogenetic congeners (19-20), and nineteen known analogues (21-39), were isolated from the stem barks of Garcinia yunnanensis Hu. All of these isolates are decorated with a C-5 lavandulyl substituent. Their structures and absolute configurations were confirmed by HRESIMS, 1D & 2D NMR spectroscopic analysis, quantum chemical calculations of electronic circular dichroism data, and single-crystal X-ray diffraction analysis. The X-ray crystallographic data of ten isolated caged compounds ascertained the absolute configuration of C-23 in the lavandulyl as S. The cytotoxicity on three cancer cell lines and the anti-nonalcoholic steatohepatitis activity of the isolates were tested. In a free fatty acid-induced L02 cell model, compounds 33 and 39 decreased intracellular lipid accumulation significantly., Competing Interests: Declaration of competing interest All authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Seven pairs of undescribed monoterpenoid polyprenylated acylphloroglucinol enantiomers [(±)-hypermonanones A-G (1-7)], together with three known analogues, were identified from the whole plant of Hypericum monanthemum Hook. The structures of these compounds were determined by analyses of their UV, HRESIMS, 1D/2D NMR spectroscopic data, and NMR calculations. The absolute configurations of these compounds were assigned by ECD calculations after chiral HPLC separation. Diverse monoterpene moieties were fused at C-3/C-4 of the dearomatized acylphloroglucinol core, which led to 3,4-dihydro-2H-pyran-integrated angular or linear type 6/6/6 tricyclic skeletons in 1-7. Compounds (-)-2 and (+)-2 exhibited significant NO inhibitory activity against LPS induced RAW264.7 cells with the IC 50 values of 7.07 ± 1.02 μM and 11.39 ± 0.24 μM, respectively., Competing Interests: Declaration of competing interest All authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Twenty-four racemic acylphloroglucinol meroterpenoids including eighteen unusual stuctures (3 ∼ 10, 13, 14, and 17 ∼ 24), and a major component filixic acid ABA (25), were isolated from Dryopteris crassirhizoma. Structurally, the dimeric acylphloroglucinol derivatives possess unprecedented skeletons of mixed acylphloroglucinol and sesquiterpene biosynthetic origin. The stereochemistries of six reported meroterpenoids with undefined chiral centers were reassigned. Two intriguing methods by analyzing a) the regularity of chemical shift variation of protons and carbons around the stereogenic centers, and b) pyridine-induced deshielding effect of hydroxy groups, to discriminate relative configurations of flexible long-chain alcohol with chiral centers separated by three or seven covalent bonds, were successfully applied. A non-enzymatic biosynthesis of 1 ∼ 24 was assumed based on a rare single-crystal cluster formed with two diastereomeric enantiomer pairs (±1/±2) and chiral HPLC analyses. Meroterpenoids 13 and 14 showed obvious inhibitory effects on NO production in LPS-induced RAW264.7, and suppressed the expression of iNOS, COX-2, IL-1β, and IL-18. Their anti-inflammatory activity was closely related to the inhibition of the formation and function of inflammasomes. Additionally, the known 25 showed antiviral efficacy against the influenza viruse A/Puerto Rico/8/1934 (H1N1)., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Alzheimer's disease (AD) diagnoses are greatly increasing in frequency as the global population ages, highlighting an urgent need for new anti-AD strategies. With the aim to search for human acetylcholinesterase (hAChE) inhibitors from the species of Myrtaceae family, ten acylphloroglucinol trimers (APTs), including eight new APTs, callistemontrimers A-H (1a, 1b, 2a, 2b, 3a, 3b, 4b, and 5b), and two naturally occurring ones (4a and 5a), along with one reported triketone-acylphloroglucinol-monoterpene adduct (6), were obtained and structurally characterized from the hAChE inhibitory acetone extract of Callistemon salignus seeds. The structures and their absolute configurations for new APTs were unequivocally established via the detailed interpretation of extensive spectroscopic data (HRESIMS and NMR), ECD calculations, and single crystal X-ray diffraction, whereas the absolute configurations of known APTs were determined by further chiral separation, and calculated ECD calculations. The results of hAChE inhibitory assay revealed that an enantiomeric mixture of 2a/2b, 2a, and 2b are good hAChE inhibitors with IC 50 values of 1.22 ± 0.23, 2.28 ± 0.19, and 4.96 ± 0.39 μM, respectively. Molecular docking was used to uncover the modes of interactions for bioactive compounds with the active site of hAChE. In addition, 2 and 6 displayed moderate neurite outgrowth-promoting effects with differentiation rates of 6.16% and 6.19% at a concentration of 1.0 μM, respectively., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Five new spirocyclic polycyclic polyprenylated acylphloroglucinols, Hyperpatulones C-G (1-5), were obtained from the leaves of Hypericum patulum. Their structures were characterized by the comprehensive analysis of their IR, NMR, CD spectra and HRESIMS data. All the new compounds were evaluated for the α-glycosidase inhibitory activities. Among them, compounds 3-5 showed α-glucosidase inhibitory activities, with IC 50 values of 14.06-37.69 μM., (Copyright © 2021. Published by Elsevier B.V.)

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., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Eucalyptus is a large genus of the Myrtaceae family with high value in various fields of industry. Recently, attention has been focused on the functional properties of Eucalyptus extracts. These extracts have been traditionally used to combat various infectious diseases, and volatile oils are usually considered to play a major role. But the positive effects of non-volatile acylphloroglucinols, a class of specialized metabolites with relatively high content in Eucalyptus, should not be neglected. Herein, non-volatile acylphloroglucinols from leaves of Eucalyptus robusta were evaluated for their abilities to inhibit Zika virus (ZIKV) which is associated with severe neurological damage and complications. The results showed eucalyprobusone G, a new symmetrical acylphloroglucinol dimer, possessed the significant ability to inhibit ZIKV without inducing cytotoxicity. The EC 50 values of eucalyprobusone G against the African lineage (MR766) and Asian lineage (SZ-WIV01) of ZIKV were 0.43 ± 0.08 and 10.10 ± 3.84 μM which were 110 times and 5.8 times better than those of the reference compound ribavirin, respectively. Further action mode research showed that eucalyprobusone G impairs the viral binding and RdRp activity of NS5. The results broaden the functional properties of Eucalyptus robusta and indicate acylphloroglucinol dimers could be developed as anti-ZIKV agents., (Copyright © 2021 Elsevier Inc. All rights reserved.)

By various chromatographic methods, 30 phloroglucinols (1-30) were isolated from a methanol extract of Dryopteris crassirhizoma, including two new dimeric phloroglucinols (13 and 25). The structures of the isolates were confirmed by HR-MS, 1D, and 2D NMR as well as by comparison with the literature. The protein tyrosine phosphatase 1B (PTP1B) effects of the isolated compounds (1-30) were evaluated using sodium orthovanadate and ursolic acid as a positive control. Among them, trimeric phloroglucinols 26-28 significantly exhibited the PTP1B inhibitory effects with the IC 50 values of 1.19 ± 0.13, 1.00 ± 0.04, 1.23 ± 0.05 μM, respectively. In addition, the kinetic analysis revealed compounds 26-28 acted as competitive inhibitors against PTP1B enzyme with K i values of 0.63, 0.61, 1.57 μM, respectively. Molecular docking simulations were performed to demonstrate that these active compounds can bind with the catalytic sites of PTP1B with negative binding energies and the results are in accordance with that of the kinetic studies. In vitro and in silico results suggest that D. crassirhizoma rhizomes together with compounds 26-28 are potential candidates for treating type 2 diabetes., (Copyright © 2021. Published by Elsevier B.V.)

Eleven new polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperwilsones A-K (1-11), along with five known PPAPs (12-16), were isolated from Hypericum wilsonii. Their structures were established via spectroscopic methods, the careful analysis of calculated and experimental electronic circular dichroism (ECD) spectra, single-crystal X-ray diffraction, the modified Mosher's method, and [Rh 2 (OCOCF 3 ) 4 ]-induced ECD. Hyperwilsone A (1) and hyperwilsone B (2) possessed the unique acetal functionality. Hyperwilsone C (3) was a rare example of [3.3.1]-type PPAP possessing a 3-isopropylfuran moiety. In bioassay, compounds 9 and 10 showed potent anti-inflammatory activity against LPS-induced NO production by inhibiting the nuclear translocation of NF-κB p65 and thus reducing the production of proinflammatory cytokines. Compounds 5, 8, 11, and 14 exhibited moderate inhibitory activity against SUDHL-4 and HL60 cancer cells with IC 50 values in the range of 5.74-19.82 μM., (Copyright © 2021 Elsevier Inc. All rights reserved.)

α-Hemolysin (Hla) is an extracellular protein secreted by methicillin-resistant Staphylococcus aureus (MRSA) strains that plays a critical role in the pathogenesis of pulmonary, intraperitoneal, intramammary, and corneal infections, rendering Hla a potential therapeutic target. In this study, 10 unreported polycyclic polyprenylated acylphloroglucinol (PPAP) derivatives, garciyunnanins C-L (1-10), with diverse skeletons, were isolated from Garcinia yunnanensis Hu. The structures of these new compounds were determined by HRMS, NMR, electronic circular dichroism (ECD) calculations, single-crystal X-ray diffraction, and biomimetic transformation. Garciyunnanins C and D (1 and 2) were found to be potent Hla inhibitors in the anti-virulence efficacy evaluation against MRSA strain., (Copyright © 2021. Published by Elsevier Inc.)

Hyperformitins A-I (1-9), nine undescribed polycyclic polyprenylated acylphloroglucinols (PPAPs) with double-bond migration, along with four new isomers hyperformitins J-M (10-13), were isolated from Hypericum perforatum. Their structures and absolute configurations were determined by spectroscopic analyses including HRESIMS, IR, UV, NMR, and ECD, as well as optical rotation (OR) calculations. The absolute configurations of previously reported analogues, garsubellins D and C as well as garcinielliptones L and M, were assigned for the first time by NMR spectra and specific rotations analyses assisting with OR calculations. Selected compounds were tested for their immunosuppressive activities against lipopolysaccharide (LPS)-induced B lymphocyte proliferation. Compounds 1, 3, 4, 5, 7, and 11 showed inhibition activities against the proliferation of B lymphocyte with IC 50 values ranging from 4.1 to 9.7 μM. Furthermore, the neuroprotective activities of the isolates against corticosterone (CORT)-induced injury in PC12 cells were also tested, and compounds 1, 12, and 13 exhibited neuroprotective effects with cell viabilities of 68.0%, 71.3%, and 68.4%, respectively under the concentration of 10 μM., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Ferroptosis is a new type of cell death, which involves central neuronal system. Inhibition of ferroptosis is a promising strategy to prevent and treat neurological diseases. Thirteen phloroglucinols (1-13) were obtained from the whole plants of Hypericum japonicum. Of them, compounds 1-3 are new ones. Their structures were elucidated by extensive analysis of spectroscopic data and X-ray diffraction. All the isolates were evaluated for their inhibitory effect on RSL3-induced ferroptosis. Two new compounds 2-3 showed significant inhibitory effect with EC 50 of 0.48 ± 0.14 μM and 0.94 ± 0.14 μM, respectively. DPPH free radical scavenging abilities of all compounds were assessed to evaluate their antioxidant effect. This work first reports the anti-ferroptosis activity of phloroglucinols., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Three new polyprenylated acylphloroglucinol meroterpenoids, hyperiforins A-C (1-3), were isolated from Hypericum forrestii (Chittenden) N. Robson, together with twelve known analogues (4-15). Their structures were established by extensive physical and spectroscopic data analysis. Compounds 1, 2, 5, 7, and 13-15 showed potent inhibitory effects on protein tyrosine phosphatase 1B with IC 50 values from 6.63 ± 2.40 to 14.21 ± 3.51 μM., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Five new 2-nor-bicyclic polyprenylated acylphloroglucinols (BPAPs), norhyperpalums A-E (1-5), three new 2,3-nor-BPAPs, norhyperpalums F-H (8-10), one new 2,3,4-nor-BPAP (13), and four known analogs (6, 7, 11 and 12) were obtained from Hypericum patulum. Their structures were confirmed by spectroscopic data, electronic circular dichroism (ECD) calculations and comparisons, quantum-chemical 13 C NMR calculations with DP4 + probability analysis, the modified Mosher's method, Rh 2 (OCOCF 3 ) 4 -induced ECD, and X-ray crystallographic data. Norhyperpalums A-E (1-5) are rare 2-nor-BPAPs bearing a 6/5/5 system based on a hexacyclic-fused 1,6-dioxaspiro[4.4]nonane core, and norhyperpalums F and G (8 and 9) exhibit an unusual 6-oxabicyclo[3.2.1]octane architecture. More significantly, compound 2 displayed pronounced cytotoxicities against hepatoma cell lines by the induction of S-phase cell cycle arrest and promotion of cell apoptosis., (Copyright © 2021 Elsevier Inc. All rights reserved.)

In our screening program for new biologically active secondary metabolites, nine new polycyclic polyprenyled acylphloroglucinols, hyperscabins D-L, together with three known compounds, were obtained from the aerial parts of Hypericum scabrum. The chemical structures of 1-9 were characterized by extensive spectroscopic analyses, nuclear magnetic resonance calculation with DP4+ probability analysis, and the electronic circular dichroism spectra were calculated. Compound 1 was an unusual prenylated acylphloroglucinol decorated with a 5-oxaspiro [4,5] deca-1,9-dione skeleton. Compound 2 was a newly identified spirocyclic polyprenylated acylphloroglucinol possessing a rare 5,5-spiroketal segment. Compounds 3, 8, and 10 (10 μM) exhibited pronounced hepatoprotective activity against d-galactosamine-induced WB-F344 cell damage in vitro assays. All test compounds (1, 3, and 7-12) demonstrated potential inhibitory effects at 10 μM against noradrenalinet ([ 3 H]-NE) reuptake in rat brain synaptosome., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Hyperelodione D (1), an undescribed polyprenylated phloroglucinol derivative possessing 6/6/5/5 fused tetracyclic core, together with hyperelodiones E-F (2-3), two unreported analogues bearing 6/5/5 fused tricyclic structure, were isolated from Hypericum elodeoides Choisy. Their planar structures were elucidated by spectroscopic analysis (HRESIMS, 1D and 2D NMR) and their absolute configurations were determined by comparison of experimental and calculated ECD data. The cytotoxicity and retinoid X receptor-α (RXRα) related activities of the isolates were evaluated and the plausible biogenetic pathways of 1-3 were proposed., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Acylphloroglucinol meroterpenoids are adducts of the acylphloroglucinol unit and polyprenylated fragments (terpenoids) with attractive structures and bioactivities. During study of the medicinal molecules of the genus Hypericum, the first example of dimethylated acylphloroglucinol meroterpenoids with pyran-fused 6/6/6 tricyclic skeletons ((+)/(-)-elodeoidols A-F (1-6)), along with three biogenetical homologues (7-9) were isolated from the herbaceous plant of Hypericum elodeoides. Their structures including absolute configurations were then identified by nuclear magnetic resonance (NMR), high resolution electrospray ionization mass spectroscopy (HRESIMS), electronic circular dichroism (ECD) analysis and calculations. The monoterpene moiety of 1-6 were cyclized as two cyclohexanes and fused with a dimethylated acylphloroglucinol unit through an additional ether linkage, which led to an interesting pyran-fused linear or angle type 6/6/6 tricyclic skeleton. Compounds 5, 8 and 9 showed preferable antibacterial activities against three oral bacteria, among the MIC value of (+)-5 was 6.25 μg/ml; Compounds 3, 7 and 8 exhibited significant NO inhibitory activity against LPS induced RAW264.7 cells (IC 50 : 10.39 ± 0.49 ~ 34.25 ± 2.32 μM)., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Hookerianones A - E (1-5), five new polyprenylated acylphloroglucinols (PPAPs), along with six known ones, were isolated from the aerial parts of Hypericum hookerianum. Their structures were elucidated by analyses of MS, NMR, chiroptical properties, biogenetic pathway, and/or single crystal X-ray diffraction. A ubiquitin-rhodamine 110 assay showed that furohyperforin and hypercalin C, two representative PPAPs in this plant, inhibited more than 90% USP7 at the concentration of 10 μM., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Eleven new acylphloroglucinols, including six new formylated phloroglucinol-monoterpene meroterpenoids, eucalyprobusals A-F (1-6), one monomeric acylphloroglucinol, eucalyprobusone B (7), and four dimeric acylphloroglucinols, eucalyprobusones C-F (8-11) were purified from the fruits of Eucalyptus robusta. The establishment of the structures of 1-11 was achieved by a combination of NMR and HRESIMS data analyses, electron circular dichroism (ECD), and single-crystal X-ray diffraction. Compounds 6, 8, and an inseparable mixture of 10 and 11 were found to be potent AChE inhibitors with IC 50 values of 3.22 ± 0.36, 3.82 ± 0.22, and 2.55 ± 0.28 μΜ, respectively. Possible interaction sites of 6, 8, 10, and 11 with AChE were investigated by means of molecular docking studies, and the results revealed that AChE residues Asn87, Ser125, Thr83, Tyr133, Tyr124, Tyr337, and Tyr341 played crucial roles in the observed activity of the aforementioned compounds., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Six new terpenoids (1-6) and two new phloroglucinol glucosides (7 and 8) were isolated from the extract of Syzygium szemaoense leaves. Among the isolates, compounds 1 and 2 (named syzygiumursanolides A and B) were unusual 28-norursane type triterpenoids with 19(18→17)-abeo spirocyclic skeleton. And syzygiumone B (8) was rare ascorbyl-modified phloroglucinol glucoside. Their structures were elucidated on the basis of comprehensive 1D and 2D NMR, HRESIMS spectroscopic data analysis, as well as experimental and calculated ECD spectra and acid hydrolysis. Antimicrobial bioassay revealed that syzygiumursanolide D (4) displayed the most potent antifungal activities with MIC values ranging from 6.25 to 25 μg/mL against a panel of fungi., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Three undescribed polycyclic polyprenylated acylphloroglucinols (PPAPs) and three tocotrienols derivatives, named as paucinochymol A-F (1-3 and 10-12), together with six known PPAPs, were isolated from the fruits of Garcinia paucinervis. Their structures and absolute configurations were determined by extensive NMR analysis and electronic circular dichroism (ECD) calculation methods. Paucinochymol A (1) is the first compound of this type featuring a ω-isogeranyl with tetrahydrofuran unit at C-1. Paucinochymols D and E (4-5) belong to rare tocotrienol with one glorious macrocyclic and an ortho-quinone moiety, respectively. The antiproliferative and anti-inflammatory activities of all isolates were tested. Four PPAPs exhibited weak inhibitory activities against three human cancer cell lines (HepG2, T98, MCF-7) with IC 50 values ranging from 10.0 to 16.0 μM. Paucinochymol D (10) displayed moderate inhibitory effects against nitric oxide (NO) production with the IC 50 value of 19.8 μM., Competing Interests: Declaration of Competing Interest There are no conflicts to declare., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Three new acylphloroglucinol glucosides, rhodosides A-C (1-3), and three known ones (4-6) were isolated from the roots of Lysidice rhodostegia. The new structures were identified by MS, NMR, and acid hydrolysis. In addition, the antioxidant capacities of the isolated compounds were evaluated using DPPH radical-scavenging assay, and compounds 1-6 exhibited obvious antioxidant activities with IC 50 values of 24.65 ± 1.27 to 38.11 ± 1.35 μM., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Phytochemical investigation of the Australian rainforest plant leaves Waterhousia mulgraveana, yielded two rare oxidized xanthenes, mulgravanols A (1) and B (2) along with a new phloroglucinol, mulgravanol C (3). Mulgravanol A (1) is the first reported example of a complex xanthene flanked by a methine bridged phloroglucinol unit. All the compounds displayed moderate inhibitory effects on nitric oxide production and TNF-α release in RAW 264.7 macrophages (IC 50 ) 42-55 μM. The structures of the new compounds were assigned based on a detailed spectroscopic interpretation., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Crown Copyright © 2020. Published by Elsevier B.V. All rights reserved.)

Six new polycyclic polyprenylated acylphloroglucinols, hyperfols CH (1-6), along with seven known ones (7-13), were isolated from the aerial parts of Hypericum perforatum. The structures were identified on the basis of comprehensive spectroscopic data analysis including 1D and 2D NMR, and the absolute configurations of the new compounds were determined by quantum chemical electronic circular dichroism (ECD) calculations. In addition, compounds 4 and 12 exhibited moderate acetylcholinesterase (AChE) inhibitory activities, with IC 50 values of 20.32 and 27.37 μM, respectively., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

A new isoiphionane sesquiterpene, named (3S, 5S, 7S, 10R)-3, 11-dihydroxyisoiphion-4-one (1), two new phloroglucinol glycosides, named eucalglobuside A (2) and eucalglobuside B (3), along with 15 known compounds were isolated from the leaves of Eucalyptus globulus. Their structures were elucidated based on extensive spectroscopic analysis and in comparison with literature data. The absolute configuration of compound 1 was determined by ECD calculation. All isolates were evaluated their inhibitory activities against the mushroom tyrosinase. As a result, three sesquiterpenoids, 1, 5β, 11-dihydroxy-iphionan-4-one (5), and (-)-globulol (8), exhibited the most potent activities with IC 50 values of 14.17 μM, 10.08 μM and 9.79 μM, respectively., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Three new prenyloxy chromanone derivatives, aucherine A-C (6, 7 and 9) as well as six known prenylated phloroglucinols (1-5 and 8) were isolated from the aerial parts of Hypericum aucheri Jaub. Et Spach. The structures of the isolated compounds were established by means of spectral techniques (HRESIMS, 1D and 2D NMR). The new compounds were tested on а panel of human tumor cell line using MTT assay. All tested compounds exerted moderate cytotoxicity with IC 50 values ranging from 19.6 to 57.8 μM. The influence of the new compounds on some key signaling molecules (procaspase-9 and Bcl-xL), implicated in the regulation of programmed cell death was assessed by Western blot analysis., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Five new homoadamantane polycyclic polyprenylated acylphloroglucinols (PPAPs, 1-5) were isolated from the fruits of Garcinia multiflora. Their structures and absolute configurations were determined by extensive spectroscopic analyses including NMR, HRESIMS and electronic circular dichroism (ECD). Compounds 1-3 possessed an unique core structure consisting of tetracyclo[7.3.1.1 3,11 .0 3,7 ]tetradecane-2,12,14- trione. In comparison with those of 1-3, compound 4 had tricyclo[4.3.1.1 3,8 ]undecane- 2,9,11-trione with the loss of prenyl unit. Garcimultinone C (5) was the first example of seco-homoadamantane-type PPAPs with 5-oxatricyclo[7.3.1.0 3,7 ]tridecane skeleton derived from C(4)/C(5) carbon-carbon bond cleavage by retro-Claisen reaction., (Copyright © 2019. Published by Elsevier B.V.)

Twelve formyl phloroglucinol meroterpenoids (FPMs) were isolated from the leaves of Eucalyptus robusta Smith. Their structures were elucidated via spectroscopic data analysis, the circular dichroism (CD) exciton chirality method, Rh 2 (OCOCF 3 ) 4 -induced CD experiments, and application of the Snatzke chirality rules. Eucalrobusones Q, S, and X are the first FPMs that have been identified in which the C-7' of phloroglucinol is linked to the C-15 of cadinane, the C-4 of cubebane, and the C-8 of menthane, respectively. (+)-Eucalrobusone X exhibited the most potent antifungal ability against Candida albicans with a MIC 50 value of 10.78 μg/mL, and eucalrobusone U exhibited the greatest anti-C. glabrata activity with MIC 50 value of 1.53 μg/mL., (Copyright © 2019. Published by Elsevier Ltd.)

Hookeriones I-Q (1-9), nine new homo-adamantane type polycyclic polyprenylated acylphloroglucinols (PPAPs), were isolated from Hypericum hookerianum, along with twenty known analogues. These structures were determined on the basis of comprehensive NMR and MS spectroscopic data. Comprehensive analysis of the NMR data revealed the correlations between the configuration of H-18 and H-28 and the chemical shifts of related signals. The cytotoxicity and anti-allergic activities of the new isolates were evaluated, and several ones exhibited moderate cytotoxicity against ECA-109 cell lines., (Copyright © 2018 Elsevier B.V. All rights reserved.)

A phytochemical study on the aerial parts of Hypericum elatoides led to the isolation of a previously undescribed polycyclic polyprenylated acylphloroglucinol derivative, hyperelatone A, seven previously undescribed phenolic metabolites, hyperelatones B-H, along with ten known analogues. The structures of hyperelatones A-H were elucidated by 1D and 2D NMR spectroscopy, HRESIMS experiment, single-crystal X-ray diffraction and comparison of experimental and calculated ECD spectra, as well as chemical derivatization. All compounds were evaluated for their neuroprotective activity against hydrogen peroxide (H 2 O 2 )-induced cell injury in rat pheochromocytoma PC-12 cells and inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in BV-2 microglial cells. Hyperelatones B-D and H, cinchonain Ib, and tenuiside A showed noticeable neuroprotection at concentrations of 1.0-100.0 μM. Hyperelatones D, G, and H, (-)-epicatechin, tenuiside A, and (Z)-3-hexenyl-β-D-glucopyranoside exhibited significant anti-neuroinflammatory activity with IC 50 values ranging from 0.75 ± 0.02 to 5.83 ± 0.23 μM., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Hyperbeanols F-Q, which are twelve undescribed monoterpenoid polyprenylated acylphloroglucinols, and four known analogues were isolated from the dried flowers of Hypericum beanii. Their structures were elucidated by detailed HRESIMS and 1D and 2D NMR data analyses. The absolute configurations of hyperbeanols FH were established by the circular dichroism (CD) exciton chirality method. The plausible biosynthetic pathway speculation of hyperbeanols F-Q indicated that diverse reactions, including prenylation, 1,6-ene reaction, rearrangement, epoxidation and dehydration, contributed to their diverse skeletons. Hyperbeanols FI, O and hypercalin B exhibited moderate nitric oxide (NO) inhibitory activities in LPS-induced RAW 264.7 macrophages, with IC 50 values in the range of 17.11-28.74 μM., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Usually isolated from Garcinia (Clusiaceae) or Hypericum (Hypericaceae) species, some Polycyclic Polyprenylated AcylPhloroglucinols (PPAPs) have been recently reported as potential research tools for immunotherapy. Aiming at exploring the chemodiversity of PPAPs amongst Garcinia genus, a dereplication process suitable for such natural compounds has been developed. Although less sensitive than mass spectrometry, NMR spectroscopy is perfectly reproducible and allows stereoisomers distinction, justifying the development of 13 C-NMR strategies. Dereplication requires the use of databases (DBs). To define if predicted DBs were accurate enough as dereplication tools, experimental and predicted δ C of natural products usually isolated from Clusiaceae were compared. The ACD/Labs commercial software allowed to predict 73% of δ C in a 1.25 ppm range around the experimental values. Consequently, with these parameters, the major PPAPs from a Garcinia bancana extract were successfully identified using a predicted DB., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Five new phloroglucinol derivatives (1-5) together with one known analogue (6) were isolated from the leaves of Syzygium austroyunnanense which is an edible folk medicine used for the treatment of diabetes. The new structures were elucidated as austroyunones A - E (1-5) by means of the extensive spectroscopic analyses including high-resolution electrospray ionization mass spectrometry (HRESIMS) and 1D and 2D nuclear magnetic resonance (NMR). Compounds 4-6 showed obvious protein tyrosine phosphatase 1B (PTP1B) inhibitory activity. This discovery of new phloroglucinols and their bioactivities provided a scientific basis for the application of S. austroyunnanense as an edible and medicinal plant., (Copyright © 2018. Published by Elsevier B.V.)

A pair of epimer brachyanins A (1) and B (2), along with a new phloroglucinol brachyanin C (3), were isolated from the leaves of Leptospermum brachyandrum. Brachyanins A (1) and B (2) were the first example of novel meroterpenoid with a unique skeleton that combined a synacrpic acid and a pinene units via a benzyl moiety. Their structures were elucidated through the application of extensive spectroscopic measurements and single-crystal X-ray diffraction analysis and with the absolute configurations of 1 and 2 were confirmed by the quantum chemical CD calculation. The hetero Diels-Alder as the key biotransformation was proposed to account for the biosynthesis of brachyanins A and B sheding light by the potential procursor brachyanin C., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Four new cinnamoyl-phloroglucinols (1-4) were isolated from the leaves of Xanthostemon chrysanthus. Compounds 1 and 2 represent the first example of natural phloroglucinols with an oxazole unit. Their structures were elucidated on the basis of NMR spectroscopic data and single crystal X-ray diffraction. Compound 3 showed moderate cytotoxic activity against MDA-MB-231 and SGC-7901 cells with IC 50 values of 25.26 ± 0.35 μM and 31.2 ± 0.94 μM, respectively., (Copyright © 2018. Published by Elsevier B.V.)

A phytochemical investigation of the aerial parts of Hypericum annulatum Moris led to the isolation of five new prenylated acylphloroglucinol derivatives hyperannulatins A-E (1-3, 5 and 7) in addition to the known hypercalyxone A (4) and 3-geranyl-1-(2'-methylpropanoyl)phloroglucinol (6). The structures were determined by 1D and 2D NMR and MS spectroscopic techniques. Compounds 1 and 2 have in their structure evgenyl group, a rare hydrocarbon side chain. The cytotoxicity of isolated compounds was established on a panel of tumor cell lines (HL-60, HL-60/DOX, MDA-MB, SKW-3 and K-562) and was determined using MTT based assays. The compounds 1 and 2 showed to be the most potent cytotoxic agents, whose IC 50 values against the chemosensitive cell lines ranged 3.42-5.87 μM and 1.48-8.21 μM, respectively. Noteworthy, albeit all tested compounds were less potent than podophyllotoxin their IC 50 values were comparable to that of the other reference drug etoposide. In some of the cell lines compounds 1 and 2 even outclassed the cytotoxicity of etoposide., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Hyperattenins L (1) and M (2), two new benzoylated polyprenylated phloroglucinol derivatives possessing unusual adamantyl and homoadamantyl core structures, were isolated from the aerial parts of Hypericum attenuatum. Their structures were determined by extensive NMR spectroscopic methods. Compound 1 possesses an unusual tetracyclo[6.3.1.1 1,10 .0 1,5 ]tridecane skeleton, representing the second report of natural product with this carbon skeleton. Compound 2 features an unexpected 2,3,13-trioxapentacyclo[7.5.3.1 7,11 .0 5,16 .0 12,16 ]octodecane ring system formed by the fusion of 2,3,8-trioxabicyclo[4.3.1]decane moiety to the tricycle[4.3.1.1 3,8 ]undecane core. Both compounds were evaluated for their cytotoxic activities against five human cancer cell lines and compound 1 showed excellent inhibitory activities against HL-60, A-549, and MCF-7 cell lines with IC 50 values of 3.86, 4.34, and 5.78μM, respectively., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Seven previously undescribed compounds, including three polycyclic polyprenylated acylphloroglucinols (garcinuntins A-C), three biphenyl derivatives (garcinuntabiphenyls A-C) and a lanostane triterpene (garcinuntine), along with thirteen known compounds were isolated from the root of Garcinia nuntasaenii Ngerns. & Suddee. Their structures were elucidated on the basis of spectroscopic techniques. For garcinuntins A-C, the absolute configurations were confirmed by the combination of single X-ray crystallography and ECD calculations. Anti-HIV activity using anti-HIV-1 reverse transcriptase and syncytium inhibition assays, and cytotoxic activity against a panel of cultured mammalian cancer cell lines of isolated compounds were investigated., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Protein tyrosine phosphatase 1B (PTP1B) has been regarded asa target for the research and development of new drugs to treat type II diabetes and PTP1B inhibitors are potential lead compounds for this type of new drugs. A phytochemical investigation to obtain new PTP1B inhibitors resulted in the isolation of four new phloroglucinols, longistyliones A-D (1-4) from the aerial parts of Hypericum longistylum. The structures of 1-4 were elucidated on the basis of extensive 1D and 2D NMR spectroscopic data analysis, and the absolute configurations of these compounds were established by comparing their experimental electronic circular dichroism (ECD) spectra with those calculated by the time-dependent density functional theory method. Compounds 1-4 possess a rare polycyclic phloroglucinol skeleton. The following biological evaluation revealed that all of the compounds showed PTP1B inhibitory effects. The further molecular docking studies indicated the strong interactions between these bioactive compounds with the PTP1B protein, which revealed the possible mechanism of PTP1B inhibition of bioactive compounds. All of the results implied that these compounds are potentially useful for the treatment of type II diabetes., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Seven new phloroglucinol derivatives, uraliones L-R (1-7), were isolated from the whole plant of Hypericum urialum. The structures of new compounds were unambiguously elucidated by comprehensive spectroscopic analysis, and the absolute configurations of the vic-diol groups were determined by Mo 2 (OAc) 4 -induced electronic circular dichroism experiments. Their capability to reversal the multidrug resistance in doxorubicin-induced resistant MCF-7/DOX sublines showed that compounds 1, 5, 6, 7 exerted a potential effect of doxorubicin susceptibility., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Fourteen phloroglucinols, named hyperciumoxide A-N, and a known compound were isolated from air-dried aerial parts of Hypericum scabrum. The structures of these compounds were deduced on the basis of extensive 1D- and 2D-NMR experiments. Hepatoprotective properties against D-galactosamine-induced HL-7702 cell damage of isolated compounds were evaluated. Meanwhile, these compounds were also tested for antidepressant activity by inhibiting reuptake of tritiated serotonin ([ 3 H]-5-HT) and Noradrenalinet ([ 3 H]-NE) in rat brain synaptosomes., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The phytochemical profile, antioxidant activity and α-glucosidase inhibitory activity of Hypericum scruglii Bacchetta, Brullo et Salmeri and Hypericum hircinum L. were analyzed and compared to those of the best-known Hypericum perforatum L. Samples were prepared using three different extraction methods (maceration in 70% ethanol, extraction in MeOH/phosphate buffer and decoction), the influence of which on the metabolic profile and bioactivities are discussed. H. scruglii and H. hircinum extracted in 70% ethanol strongly inhibited α-glucosidase (IC 50 7.25 and 14.05μg/ml, respectively), which is a valuable enzymatic target for treating metabolic disorders, while H. perforatum was found to be less powerful than the other two species in all the performed biological tests. The phytochemical profile was analyzed by NMR, HPLC-DAD and HPLC-FLD, revealing remarkable differences among the species. In particular, H. scruglii, which is a species endemic to Sardinia Island (Italy), was particularly enriched in two phloroglucinol-derivatives identified by means of 2D NMR and LC/MS/MS experiments as 3-geranyl-1-(2'-methylbutanoyl)-phloroglucinol and 3-geranyl-1-(2'-methylpropanoyl)-phloroglucinol., (Copyright © 2017. Published by Elsevier B.V.)

Three new phloroglucinol derivatives, namely agripinol A-C (1-3), were isolated from Agrimonia pilosa Ledeb, along with two known ones (4-5). Their structures were characterized by spectroscopic methods, including MS and NMR spectroscopic techniques. The absolute configurations of the new compounds were unambiguously established by single crystal X-ray diffraction analyses. In the cytotoxicity assay, all compounds exhibited more potent cytotoxic activities against HCT-116, MDA-MB-231 and PC-3, as compared with the positive control fluorouracil., (Copyright © 2017. Published by Elsevier B.V.)

Callviminols A-E (1-5), five rare phloroglucinols bearing a framework embodying a hexahydrodibenzo[b,d]furan or 2-phenylcyclohexanol nucleus derived from a phloroglucinol-monoterpene adduct, were isolated from the leaves of Callistemon viminalis. Their structures were established via extensive spectroscopic measurements, with the absolute configuration of 5 determined by electronic circular dichroism (ECD) calculations. The plausible biogenetic pathway suggested that a unique oxidative radical addition and classic cationic cyclization were key biosynthetic steps., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Four new polyisoprenylated benzoylphloroglucinol derivatives, hyperscabrones J-M (1-4), were isolated from the air-dried aerial parts of Hypericum scabrum. Their structures were elucidated by spectroscopic methods and were subsequently confirmed by comparing with data of known compounds. The absolute configuration of the bicyclo[3.3.1]nonane-2,4,9-trione core was defined by the experimental and calculated electronic circular dichroism (ECD) spectra. The evaluation of their hepatoprotective activities against paracetamol-induced HepG2 cell damage showed that compounds 2 and 4 exhibited significant hepatoprotection at 10μM., (Copyright © 2016 Elsevier B.V. All rights reserved.)