Hyperatins A-D, highly oxidized polycyclic polyprenylated acylphloroglucinols from Hypericum perforatum L. with hypoglycemic potential in liver cells.

Hyperatins A-D (1-4), four previously undescribed polycyclic polyprenylated acylphloroglucinols, were isolated from Hypericum perforatum L. (St. John's wort). Compound 1 possessed a unique octahydroindeno[1,7a-b]oxirene ring system with a rare 2,7-dioxabicyclo[2.2.1]heptane fragment. Compounds 2-4 had an uncommon decahydrospiro[furan-3,7'-indeno[7,1-bc]furan] ring system. Their structures were established by spectroscopic analyses and X-ray crystallography. Plausible biosynthetic pathways of 1-4 were also proposed. Compounds 1 and 2 exerted promising hypoglycemic activity by inhibiting glycogen synthase kinase 3 expression in liver cells.

Chae-type cytochalasans from coculture of Aspergillus flavipes and Chaetomium globosum.

Cocultivation of the high cytochalasan-producing fungi Aspergillus flavipes and Chaetomium globosum resulted in the isolation of 11 undescribed Chae-type cytochalasans. Their structures were determined by spectroscopic data and NMR data calculations. Asperchaetoglobin A (1) was the first Chae-type cytochalasan possessing an unprecedented nitrogen bridge between C-17 and C-20 to generate a surprising 5/6/12/5 multiple ring system; asperchaetoglobins B and C (2 and 3) displayed higher oxidation with an additional epoxide at the thirteen-member ring; asperchaetoglobin D (4) was the second Chae-type cytochalasin featuring a 5/6/12 tricyclic ring system. The cytotoxic activities against five human cancer cell lines and antibacterial activities against Staphylococcus aureus and Colon bacillus of selected compounds were evaluated in vitro.

Undescribed α-pyrone-containing mycotoxins and an eremophilane-type sesquiterpenoid isolated from Aspergillus aureoterreus and their cytotoxicity.

Four previously undescribed and highly oxygenated α-pyrone-containing mycotoxins designated citreoviridins (E‒H), and an unreported eremophilane-type sesquiterpenoid namely aureoterrolide N, were isolated from the culture broth of Aspergillus aureoterreus. Those isolates were inferred from extensive spectroscopic methods and theoretical computation, where their absolute configurations were unambiguously determined by coupling constants following an empirical rule for the acyclic vicinal diol, theoretical ECD calculation, and NMR computation using the GIAO method and DP4+ analysis. Among them, citreoviridins E‒H are four stereoisomers of a citreoviridin derivative, featuring a methylated α-pyrone, an oxidized polyene linker, and a tetrahydrofuran ring. Cytotoxicity assay of all isolates demonstrated that aureoterrolide N exhibited weak inhibitory effect against human cancer cell line HL-60 with an inhibition rate of 55.2% at 40.0 µM.

Cytotoxic Ergosteroids from a Strain of the Fungus Talaromyces adpressus.

Nine new ergosteroids (1-9) and seven known ones (10-16) were isolated from Talaromyces adpressus. Their structures and absolute configurations were determined by the interpretation of NMR spectroscopic data, HRESIMS, ECD calculations, and single-crystal X-ray diffraction analyses. Structurally, compound 1 was an ergosteroid with two epoxy and a 3α-OH group at ring A, while compounds 8 and 9 had a contracted ring A with a peroxy bridge between C-3 and C-9, which were reported for the first time. Compounds 2-6, 9, 11, and 15 displayed cytotoxic activities with IC50 values ranging from 0.4 to 32 µM, and compound 7 exhibited an immunosuppressive effect against LPS-induced B lymphocyte proliferation with an IC50 value of 8.6 µM. The structure-activity relationships of these compounds are briefly discussed.

Asperemestrins A-D, Emestrin Hybrid Polymers with Bridged Skeletons from the Endophytic Fungus Aspergillus nidulans.

Four emestrin hybrid polymers, asperemestrins A-D (1-4, respectively), were isolated from the fungus Aspergillus nidulans. Asperemestrins A-C are the first examples of emestrin-sterigmatocystin heterodimers bearing a 7/5/6/6/5/5/6/6/6 nonacyclic system with a 2,5-diazabicyclo[2.2.2]octane-3,6-dione core, while asperemestrin D features an unprecedented 2,15-dithia-17,19-diazabicyclo[14.2.2]icosa-4,8-diene-12,18,20-trione core skeleton. Their structures were determined by extensive spectroscopic data, electronic circular dichroism calculations, and single-crystal X-ray diffraction. Asperemestrin B showed moderate cytotoxicity against cancer cell lines, including SU-DHL-2, HEPG2, and HL-60.

Aureoterrolides B‒M: Eremophilane-type sesquiterpenoids isolated from Aspergillus aureoterreus and their cytotoxicity.

Uncovered by genome sequence analyses, twelve undescribed sesquiterpenoids designated aureoterrolides B‒M, were isolated from the culture broth of the fungus Aspergillus aureoterreus together with two known analogues. They are unusual eremophilanes with an oxidized C-4, of which aureoterrolide J is an unreported furanoeremophilane comprising a 3/6/6/5/3 pentacyclic architecture with a rare 3,6-spiro ring system. Their structures and absolute configurations were unambiguously assigned by extensive spectroscopic method and theoretical ECD calculation. All isolated compounds were evaluated their cytotoxicity, and aureoterrolides A, B, and I-K showed moderate cytotoxic activity against three human cancer cell lines (HL-60, HepG-2, and SKOV-3) with IC50 values ranging from 4.53 ± 0.05 to 24.71 ± 0.16 µM. Among them, aureoterrolide A exhibited activity such close to the positive control and apoptotic effect on HL-60 cells at a concentration of 5.0 µM.

Four undescribed ergostane-type steroids from Lasiodiplodia pseudotheobromae and their neuroprotective activity.

Four undescribed ergostane-type steroids, (22E,24R)-4α,5α-epoxyergosta-9α,14ß-dihydroxy-7,22-diene-3,6-dione, (22E,24R)-4α,5α-epoxyergosta-9α,14α-dihydroxy-7,22-diene-3,6-dione, 12α-hydroxyergosta-7,22,24(28)-triene-3-one, and 3ß,12α-dihydroxyergosta-7,24(28)-diene, along with a known congener (22E,24R)-9α,14ß-dihydroxyergosta-4,7,22-triene-3,6-dione, were isolated from the fungus Lasiodiplodia pseudotheobromae. Their structures were elucidated using NMR, HRESIMS, ECD calculation, and X-ray diffraction analyses. (22E,24R)-4α,5α-epoxyergosta-9α,14ß-dihydroxy-7,22-diene-3,6-dione and (22E,24R)-4α,5α-epoxyergosta-9α,14α-dihydroxy-7,22-diene-3,6-dione are a pair of C-14 epimers possessing an unusual epoxy group between C-4 and C-5, which was demonstrated using single-crystal X-ray diffraction analyses. The absolute configurations of 12α-hydroxyergosta-7,22,24(28)-triene-3-one and 3ß,12α-dihydroxyergosta-7,24(28)-diene were determined by ECD calculations. Moreover, 3ß,12α-dihydroxyergosta-7,24(28)-diene exhibited neuroprotective activity in vitro in glutamate-treated SH-SY5Y cell lines.

30-norlanostane triterpenoids and steroid derivatives from the endophytic fungus Aspergillus nidulans.

Two undescribed 30-norlanostane triterpenoids, named nidulanoids A and B, one ergostane-type steroid with an unusual double bond between C-17 and C-20 designated (17E,22E,24R)-3ß,5α-dihydroxyergosta-7,17,22-trien-6,16-dione, and one pregnane, (7Z,9Z,17Z)-,2α,3ß-dihydroxypregna-7,9,17 (20)-trien-18-al, along with six known steroids were isolated from the extract of the fungus Aspergillus nidulans. Among them, nidulanosides A and B represents the first example of naturally occurred 30-norlanostane triterpenoids featuring a C9 side-chain moiety at C-17 and a hemiacetal system formed between C-3 and C-19, as an intermediate between lanostane and the regular steriods; the structure of (17E,22E,24R)-3ß,5α-dihydroxyergosta-7,17,22-trien-6,16-dione possesses an untypical Δ17,20 double bond; meanwhile, (7Z,9Z,17Z)-,2α,3ß-dihydroxypregna-7,9,17 (20)-trien-18-al represents the first example of C-21 steroid with an aldehyde group at C-13. Their structures and absolute stereochemistry were elucidated based on spectroscopic data, electronic circular dichroism (ECD) calculations, and single-crystal X-ray diffraction analysis. (7Z,9Z,17Z)-,2α,3ß-dihydroxypregna-7,9,17 (20)-trien-18-al showed moderate inhibitory activities against rat brain cancer (PC12) cell lines, with IC50 value of 7.34 µM. This study enriches the diversified structures of triterpenoids and steroids analogues from A. nidulans and indicated (7Z,9Z,17Z)-,2α,3ß-dihydroxypregna-7,9,17(20)-trien-18-al to be a promising lead compound against PC12 cell lines.

Armochaetoglasins J and K: new cytochalasans from Chaetomium globosum.

Two novel cytochalasans, armochaetoglasin J (1) and armochaetoglasin K (2), along with 14 known analogues (3-16) were isolated from Chaetomium globosum. Their structures were elucidated by HRESIMS, NMR spectroscopy, single-crystal X-ray crystallography, and ECD spectra. Armochaetoglasins J and K were found to be inactive against the HepG2, HT-29, K562, HL-60, and A549 cancer cell lines.

Multioxidized aromatic polyketides produced by a soil-derived fungus Penicillium canescens.

Under OSMAC strategy, seven unreported multioxidized aromatic polyketides, penicanesins A‒G, were discovered from a soil-derived fungus Penicillium canescens along with seven known compounds. Their structures were assigned by extensive 1D and 2D NMR spectra in combination with HRESIMS and single crystal X-ray diffraction. Absolute stereochemistry of penicanesins A and D were elucidated by theoretical ECD calculation. (±)-Penicanesins A and B are two pairs of racemic aromatic polyketides with an unusual 6/6/6/6 heterotetracyclic ring core. In bioassay, (-)-penicanesin A shows potential cytotoxicity against human cancer cell lines HL-60 and SW480 with IC50 values at 13.8 ± 0.6 and 12.5 ± 0.9 µM, respectively, whereas the enantiomer (+)-penicanesin A is less active.

Unprecedented polycyclic polyprenylated acylphloroglucinols with anti-Alzheimer's activity from St. John's wort.

Hyperforones A-J (1-10), ten degraded and reconstructed polycyclic polyprenylated acylphloroglucinols (PPAPs) with six different types of unusual architectures, were isolated from Hypericum perforatum (St. John's wort). Compound 1 is characterized by an unprecedented 1,5-epoxyfuro[3',4':1,5]cyclopenta[1,2-c]oxecine ring system; compounds 2 and 3 represent the first PPAPs with a contracted B-ring leading to the unique 5/5 core skeletons; compound 4, a proposed biosynthetic precursor of 2, is defined by an oxonane-2,7-dione architecture; compound 5 features an unusual spiro[furo[3',4':1,5]cyclopenta[1,2-b]oxepine-3,2'-oxetane] ring system; compounds 6-8 possess a rare macrocyclic lactone ring in addition to the newly formed C-ring; and compounds 9 and 10 contain a newly formed six-membered C-ring, which constructed the unexpected 6/6 scaffold with the B-ring. Hypothetic biosynthetic pathways to generate these scaffolds starting from the classic [3.3.1]-type PPAPs helped to elucidate their origins and validate their structural assignments. Compounds 4 and 6 simultaneously displayed notable activation of PP2A (EC50: 258.8 and 199.0 nM, respectively) and inhibition of BACE1 in cells (IC50: 136.2 and 98.6 nM, respectively), and showed better activities than the positive controls SCR1693 (a PP2A activator, EC50: 413.9 nM) and LY2811376 (a BACE1 inhibitor, IC50: 260.2 nM). Furthermore, compound 6 showed better therapeutic effects with respect to the reduction of pathological and cognitive impairments in 3 × Tg AD mice than LY2811376. Compound 6 represents the first multitargeted natural product that could activate PP2A and simultaneously inhibit BACE1, which highlights compound 6 as a promising lead compound and a versatile scaffold in AD drug development.

Spectanoids A-H: Eight undescribed sesterterpenoids from Aspergillus spectabilis.

Ten sesterterpenoids, including eight undescribed ones named spectanoids A-H and two known analogs, were obtained from Aspergillus spectabilis. Their structures, including absolute configurations, were determined based on HRESIMS, NMR, ECD calculations and single-crystal X-ray diffraction analyses. Spectanoids A-G are tricyclic sesterterpenoids with an unusual 5/12/5 ring system, while spectanoid H possesses a 5/8/6/5 ring system. All of these compounds were evaluated for their cytotoxic activities against three human cancer cells, and spectanoid A, spectanoid C and spectanoid F exhibited moderate cytotoxic activities with IC50 values ranging from 12.1 to 26.1 µM.

Polycyclic polyprenylated acylphloroglucinols with immunosuppressive activity from Hypericum perforatum and absolute configurations assignment of previously reported analogues.

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 IC50 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.

Five undescribed steroids from Talaromyces stipitatus and their cytotoxic activities against hepatoma cell lines.

Five undescribed sterol derivatives, (22E,24R)-7α-methoxy-5α,6α-epoxyergosta-8(14),22-diene-3ß,15ß-diol, (22E,24R)-5α,6α-epoxyergosta-8(14),22-diene-3ß,7ß,15α-triol, (22E,24R)-3ß,5α-dihydroxy-14ß,15ß-epoxyergosta-7,22-diene-6-one, (22E,24R)-6α-methoxy-7α,15ß-dihydroxyergosta-4,8(14),22-triene-3-one, and (25S)-ergosta-7,24(28)-diene-3ß,4α,6α,26-tetraol were isolated from the extract of Talaromyces stipitatus, along with eight known congeners. This is the first example of a class of ergosterols isolated from T. stipitatus. Their structures with absolute configurations were elucidated based on NMR spectroscopic data, ECD calculations, and X-ray crystallographic analyses. All these compounds were tested for their effects on three hepatoma cell lines including Hep3B, HepG2, and Huh-7. Moreover, (22E,24R)-5α,6α-epoxyergosta-8(14),22-diene-3ß,7ß,15α-triol and (22E,24R)-9α,15α-dihydroxyergosta-4,6,8(14),22-tetraen-3-one were further evaluated for their impacts on cell cycle progression and apoptosis due to their pronounced cytotoxicity, to uncover their underlying mechanisms. Our results suggested that their antiproliferative activities were mainly mediated by inducing cell apoptosis.

One new spirocyclic lactone and one new benzopyran derivative from Aspergillus terreus.

One new spirocyclic lactone, terreinlactone C (1), and one new benzopyran derivative, 2,2-dimethyl-3-hydroxychroman-6-aldehyde (2), were discovered from the fungus Aspergillus terreus. The chemical structures of compounds 1 and 2 were elucidated by detailedly analyzing NMR and HRESIMS data. Compound 1 is the first natural product with a 1-oxaspiro[4.5]decan-2-one ring system and a possible biogenetic pathway is proposed. Two compounds were tested for their cytotoxic activities against five human cancer cell lines.[Formula: see text].

[Adsorption of Cadmium and Arsenic by Corn Stalk Biochar Solidified Microorganism].

Immobilization of bacteria on biochar can improve the performance of the soil complex polluted with cadmium (Cd) and arsenic (As). In this study, bacteria (Delftia sp. B9, B9), biochar (corn stalks biochar, CSB), and biochar-bacteria complexes (B-CSB) were used as adsorption materials to explore the adsorption characteristics of Cd and As. The effects of pH on the adsorption performance of Cd and As and the ion removal from the aqueous solution were investigated, and the adsorption behaviors were simulated using an isothermal adsorption model. The changes in Cd and As speciation with the addition of B9, CSB, and B-CSB to As and Cd-contaminated soil were explored. The results showed that the Cd-saturated adsorption capacities of B9, CSB, and B-CSB were 49.43, 82.68, and 75.38 mg ·g-1, respectively; the As-saturated adsorption capacities were 24.67, 42.92, and 34.03 mg ·g-1, respectively. The concentration of available Cd and As significantly decreased, whereas the residual fraction increased after the addition of B-CSB. B-CSB was shown to be an effective material for the remediation of soil complexes polluted with Cd and As.

Secoemestrin C inhibits activation of NKT/conventional T cells and protects against concanavalin A-induced autoimmune hepatitis in mice.

Secoemestrin C is an epitetrathiodioxopiperazine isolated from Aspergillus nidulans, which has only been reported in terms of inhibiting tumor cell proliferation. Here, we determined the immunomodulatory and hepatoprotective effects of secoemestrin C in a mouse model of acute autoimmune hepatitis. In an in vitro assay, purified hepatic mononuclear cells (MNCs) from C57BL/6J mice were stimulated with concanavalin A (Con A) in the presence of secoemestrin C, and cell proliferation and cytokine production were measured. In an in vivo assay, mice with or without secoemestrin C pretreatment were injected with Con A to induce acute hepatitis. The secoemestrin C treatment dose-dependently suppressed cell proliferation and proinflammatory cytokine secretion in Con A-stimulated hepatic MNCs in vitro. In Con A-challenged mice, pre-injection with secoemestrin C significantly decreased the generation of proinflammatory cytokines and ameliorated liver injury. Furthermore, pretreatment with secoemestrin C significantly inhibited the Con A-induced activation of NKT and conventional T cells, and decreased IFN-γ production by these two cell populations. We conclude that secoemestrin C has an immunosuppressive effect on NKT and conventional T cells and has hepatoprotective activity in mouse autoimmune hepatitis. These findings provide new insights into the use of fungus-derived natural products for the treatment of autoimmune diseases.

Polysubstituted Phenyl Glucosides Produced by the Fungus Metarrhizium anisopliae.

Metarhizosides A-G (1-7), seven new polysubstituted phenyl glucosides, were isolated from the extracts of solid rice medium of a marine-derived fungus Metarrhizium anisopliae. Compounds 1-7 all contain a polysubstituted phenyl group and the sugar unit is identified as 4'-O-methyl-ß-D-glucopyranose. Their structures were elucidated by NMR spectroscopy and chemical method. These compounds were evaluated for anti-inflammatory activity by using LPS-stimulated murine macrophage RAW 264.7 cells and the cytotoxicities against four human cancer cell lines.

An Fe2+ - and α-Ketoglutarate-Dependent Halogenase Acts on Nucleotide Substrates.

While halogenated nucleosides are used as common anticancer and antiviral drugs, naturally occurring halogenated nucleosides are rare. Adechlorin (ade) is a 2'-chloro nucleoside natural product first identified from Actinomadura sp. ATCC 39365. However, the installation of chlorine in the ade biosynthetic pathway remains elusive. Reported herein is a Fe2+ -α-ketoglutarate halogenase AdeV that can install a chlorine atom at the C2' position of 2'-deoxyadenosine monophosphate to afford 2'-chloro-2'-deoxyadenosine monophosphate. Furthermore, 2',3'-dideoxyadenosine-5'-monophosphate and 2'-deoxyinosine-5'-monophosphate can also be converted, albeit 20-fold and 2-fold, respectively, less efficiently relative to the conversion of 2'-deoxyadenosine monophosphate. AdeV represents the first example of a Fe2+ -α-ketoglutarate-dependent halogenase that converts nucleotides into chlorinated analogues.

Prenylated quinolinone alkaloids and prenylated isoindolinone alkaloids from the fungus Aspergillus nidulans.

Two undescribed prenylated quinolinone alkaloids, aspoquinolones E and F, and three undescribed prenylated isoindolinone alkaloids aspernidines F-H, were isolated from the fungus Aspergillus nidulans. Their structures and configurations were elucidated based on spectroscopic analyses and ECD spectra. Aspoquinolones E and F possess a C10 moiety with an unusual 2,2,4-trimethyl-3oxa-bicyclo[3.1.0]hexane unit, and aspernidines F-H own a C15 side chain. These compounds were evaluated for cytotoxic activities against five human cancer cell lines, compounds 1 and 5 exhibited strong inhibitory activities against A-549 and SW-480 cells with IC50 values of 3.50 and 4.77 µM, respectively.