Experimental Electronic Circular Dichroism Spectra Research Articles

Penipyranicins A-C: Antibacterial Methylpyran Polyketides from a Hydrothermal Spring Sediment Penicillium sp.

Four new aromatic polyketides (1-4) were isolated from Penicillium sp. RO-11, obtained from the sediment of a hydrothermal spring in the southwestern region of Saudi Arabia. The new compounds are penipyranicins A-C (1-3), characterized by a 4-methyl-4H-pyran moiety, a structural motif unprecedented among fungal polyketides, and the naphthopyrone derivative isopyrenulin (4). The structures of the new compounds were elucidated on the basis of data from mass spectrometry, 1D and 2D NMR analysis, and comparison between experimental and time-dependent density functional theory-calculated electronic circular dichroism spectra. A plausible biosynthetic pathway connecting penipyranicins and isopyrenulin is proposed. The isolated compounds were active against Gram-positive and Gram-negative bacteria.

Glycosylated Phenols and an Unprecedented Diacid from the Saudi Plant Cissus rotundifolia.

Bioassay-guided investigation of the Saudi medicinal and edible plant Cissus rotundifolia yielded seven metabolites, including the new sucrose diester cissuxinoside (1) and the unprecedented cissoic acid (2), belonging to unusual classes of secondary metabolites. Their chemical structures were elucidated through a combination of HR-MS and NMR data. The absolute configuration of cissoic acid was assigned by comparison of experimental and TDDFT-calculated electronic circular dichroism spectra. In addition, three rare C-glycosyl flavones (3-5) were fully characterized, and for 3 and 4 NMR data are reported here for the first time. This study identified 1-O-(4-coumaroyl)-β-d-glucopyranose (7) as the main compound responsible for the glucose uptake stimulation effect exerted by the extract.

The phytochemical investigation of five African Croton species: Croton oligandrus, Croton megalocarpus, Croton menyharthii, Croton rivularis and Croton megalobotrys

Abstract The chemistry of five African Croton taxa, Croton oligandrus Pierre ex Hutch., Croton megalocarpus Hutch., Croton menyharthii Pax, Croton rivularis Mull.Arg. and Croton megalobotrys Mull.Arg. is described. The undescribed ent-19-hydroxyisopimara-8(9),15-dien-7-one and ent-isopimara-7(8),15-dien-16,19-diol were isolated from the fruits of C. oligandrus, ent-isopimara-7(8),15-dien-19-yl octadecanoate was obtained from both the fruits and leaves, and ent-19-hydroxyisopimara-8(9),15-dien-7-one was isolated from the leaves of this species. The undescribed 3,4,15,16-diepoxy-8α-hydroxycleroda-13(16),14-dien-12S,17-olide and (5S,9R,10S)-7,13-ent-abietadien-2-one were isolated from the leaves and roots of C. megalocarpus respectively. Compounds isolated from C. menyharthii, C. rivularis and C. megalobotrys have been reported from other sources. The structures of the compounds were determined using NMR, IR and MS experiments. The absolute configurations of the ent-isopimarane, ent-abietane and ent-clerodane diterpenoids isolated were confirmed by comparing calculated and experimental electronic circular dichroism (ECD) spectra. DP4+ probability calculations were used to assign the configuration at C-8 for 3,4,15,16-diepoxy-8α-hydroxycleroda-13(16),14-dien-12S,17-olide. Epoxy-ent-clerodadiene, 3β,4β:15,16-diepoxy-13(16),14-ent-clerodadien-17,12S-olide, 3β,4β:15,16-diepoxy-8α-hydroxy-ent-cleroda-13(16),14-dien-12,17-olide, 7,13-abietadien-2-ol, (5S,9R,10S)-7,13-ent-abietadien-2-one, crotonolide E, furocrotinsulolide A, epoxychiromodine, 3β,4β:15,16-diepoxy-13(16),14-ent-clerodadiene and crotohalimaneic acid were selected for screening based on their ability to add diversity to the NCI small molecule compound collection, and were evaluated against the NCI60 panel of human tumour cell lines at 10μM level, but found inactive.

Limonoids with diverse structures of rings-A,B from the Thai mangrove, Xylocarpus moluccensis

Nine new limonoids, named thaixylomolins S–Z (1–8) and 2-O-acetylthaixylomolin Z (9), were isolated from seeds of the mangrove, Xylocarpus moluccensis, collected in the mangrove swamp of Trang Province, Thailand. Thaixylomolin S (1) is the fourth member of the khayalactone class of limonoids containing a hexahydro-2H-2,5- propanocyclopenta[b]furan motif. Thaixylomolins T–Y (2–7) are structurally diverse mexicanolides; whereas thaixylomolin Z (8) and 2-O-acetylthaixylomolin Z (9) are phragmalin 8,9,30-orthoesters. The structures of these compounds were established by HRESIMS and extensive 1D and 2D NMR investigations. The absolute configurations of thaixylomolins S (1), U (3), and Z (8) were unambiguously established by single-crystal X-ray diffraction analyses, conducted with Cu Kα radiation; whereas that of 2-O-acetylthaixylomolin Z (9) was determined to be the same as that of thaixylomolin Z (8) by the accurate fit of their experimental electronic circular dichroism spectra. Thaixylomolin S (1), featuring the presence of a 30-(2′-methyl)butyryloxy group, is the first limonoid of the khayalactone class, whose constitution and absolute configuration are unequivocally determined by X-ray crystallography. The inhibitory activities of all the compounds, except for the epimers 4, were assayed against human carboxylesterase 2. All the tested compounds exhibited inhibition rates in the range of 16–65% at the concentration of 100.0 μM.

Characterization of a New Insecticidal Anthraquinone Derivative from an Endophyte of Acremonium vitellinum against Helicoverpa armigera.

Endophytic fungi have proven to be prolific producers of bioactive secondary metabolites with agricultural applications. In this study, bioassay-guided isolation of the endophytic fungus Acremonium vitellinum yielded four anthraquinone derivatives (compounds 1-4), including a previously undescribed dimethylated derivative of bipolarin, 6,8-di-O-methylbipolarin (1). Their structures were determined by 1D and 2D nuclear magnetic resonance analysis as well as high-resolution electrospray ionization mass spectrometry data, and the absolute configuration of 1 was established by comparing the calculated and experimental electronic circular dichroism spectra. The insecticidal activity of the isolated compounds against the cotton bollworm Helicoverpa armigera was evaluated. The new compound 1 showed the strongest larvicidal activity against the 3rd instar larvae of H. armigera with an LC50 value of 0.72 mg/mL. In addition, transcriptome sequencing was performed to evaluate the molecular mechanism of the insecticidal activity. In total, 5732 differentially expressed genes were found, among which 2904 downregulated genes and 2828 upregulated genes were mainly involved in cell autophagy, apoptosis, and DNA mismatch repair and replication. The results presented in this study reveal how 1 exerts its insecticidal effects against H. armigera via genome-wide differential gene expression analyses. Our findings suggest that anthraquinone derivatives are potential biopesticides for cotton bollworm control.

Cytochalasins from an endophytic fungus Phoma multirostrata XJ-2-1 with cell cycle arrest and TRAIL-resistance-overcoming activities

Nine new (1–9) and four known (10–13) [13]cytochalasins, along with three known 24-oxa[14]cytochalasins (14–16), were isolated from the culture of Phoma multirostrata XJ-2-1, an endophytic fungus obtained from the fibrous root of Parasenecio albus. Their structures were elucidated by interpretation of the nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass spectroscopy (HRESIMS). The absolute configurations were assigned by single-crystal X-ray crystallography, modified Mosher′s method, and by analysis of their experimental electronic circular dichroism (ECD) spectra. Compound 6 could induce cell cycle arrest at G2-phase in CT26 and A549 cells, and displayed moderate cytotoxicity against CT26 and A549 cell lines with IC50 values of 6.03 and 5.04 μM, respectively. Co-treatment of 7–9, 13 and 16 with tumor necrosis factor related apoptosis inducing ligand (TRAIL) could significantly decrease the cell viability of A549, which revealed that cytochalasins could possibly be a new group of TRAIL sensitizers in lung cancer therapy.

Discovery of a Secalonic Acid Derivative from Aspergillus aculeatus, an Endophyte of Rosa damascena Mill., Triggers Apoptosis in MDA-MB-231 Triple Negative Breast Cancer Cells.

A new secalonic acid derivative, F-7 (1), was isolated from the endophytic Aspergillus aculeatus MBT 102, associated with Rosa damascena. The planar structure of 1 was established on the basis of 1D and 2D NMR and ESI-TOF-MS spectra. The relative configuration of 1 was determined applying a combined quantum mechanical/NMR approach and, afterward, the comparison of calculated and experimental electronic circular dichroism spectra determined the assignment of its absolute configuration. The compound possesses strong cytotoxic activity against triple negative breast cancer (TNBC) cells. It was found to induce apoptosis, as evidenced by scanning electron microscopy and phase contrast microscopy. Furthermore, flow cytometry analyses demonstrated that 1 induced mitochondrial damage and reactive oxygen species mediated apoptosis, arresting the G1 phase of the cells in a dose-dependent manner. Also, the compound causes significant microtubule disruption in TNBC cells. Subsequently, 1 restricted the cell migration leading to the concomitant increase in expression of cleaved caspase and PARP.

Enantiomeric 8-O-4′-type neolignans from Crataegus pinnatifida exhibit cytotoxic effect via apoptosis and autophagy in Hep3B cells

Crataegus pinnatifida has been famous for its nutritional purpose. However, systematic investigation on the bioactive constituents is still lacking, although this fruit has been reported for its cytotoxic effect before. In this study, two pairs of new lignan enantiomers (1a/1b, 2a/2b), which isolated using chiral chromatographic column from the fruits of C. pinnatifida were studied. The absolute configurations of enantiomers were determined by comparison between the experimental electronic circular dichroism (ECD) and calculated ECD spectra. Among them, 1a/1b exhibited a better cytotoxic effect in hepatocellular carcinoma Hep3B cells with an IC50 value of 34.97 ± 2.74 and 17.42 ± 0.71 μM, respectively. In addition, 1b induced much more apoptotic, autophagic cells than 1a in Hep3B cells. Furthermore, the underlying mechanism was demonstrated that p38 activation could promote 1b-induced apoptosis and autophagy. Moreover, 1b-induced apoptosis was significantly decreased in the presence of autophagic inhibitor Bafilomycin A1 (Baf A1), suggesting that the induction of autophagy enhanced apoptotic cell death in 1b-treated cells. In general, these findings provide a valuable basis for further understanding the effect of 8-O-4′ lignans in C. pinnatifida on cytotoxic effect.

Cytotoxic Secondary Metabolites Isolated from the Marine Alga-Associated Fungus Penicillium chrysogenum LD-201810.

A new pentaketide derivative, penilactonol A (1), and two new hydroxyphenylacetic acid derivatives, (2’R)-stachyline B (2) and (2’R)-westerdijkin A (3), together with five known metabolites, bisabolane-type sesquiterpenoids 4–6 and meroterpenoids 7 and 8, were isolated from the solid culture of a marine alga-associated fungus Penicillium chrysogenum LD-201810. Their structures were elucidated based on extensive spectroscopic analyses, including 1D/2D NMR and high resolution electrospray ionization mass spectra (HRESIMS). The absolute configurations of the stereogenic carbons in 1 were determined by the (Mo2(OAc)4)-induced circular dichroism (CD) and comparison of the calculated and experimental electronic circular dichroism (ECD) spectra, while the absolute configuration of the stereogenic carbon in 2 was established using single-crystal X-ray diffraction analysis. Compounds 2 and 3 adapt the 2’R-configuration as compared to known hydroxyphenylacetic acid-derived and O-prenylated natural products. The cytotoxicity of 1–8 against human carcinoma cell lines (A549, BT-549, HeLa, HepG2, MCF-7, and THP-1) was evaluated. Compound 3 exhibited cytotoxicity to the HepG2 cell line with an IC50 value of 22.0 μM. Furthermore, 5 showed considerable activities against A549 and THP-1 cell lines with IC50 values of 21.2 and 18.2 μM, respectively.

Epipolythiodiketopiperazine and trichothecene derivatives from the NaI-containing fermentation of marine-derived Trichoderma cf. brevicompactum.

The marine-derived fungus Trichoderma sp. TPU199 (cf. Trichoderma brevicompactum) produces pretrichodermamide A (1) and gliovirin (2), which possess a rare type of epipolythiodiketopiperazine (ETP) structure with a disulfide bridge between the α- and β-positions of two amino acid residues. We previously reported that this strain gave the halogenated ETPs, DC1149B (4), DC1149R (6), and iododithiobrevamide (7), when fermented with sodium halides (NaCl, NaBr, and NaI). Further analyses of the metabolites obtained under NaI-containing culture conditions resulted in the isolation of two new ETP derivatives (11 and 12) and three new trichothecene sesquiterpenes (13-15). The structures of 11 and 12, including their absolute configurations, were elucidated based on spectroscopic data for 11 and 12 and comparisons with those for 1 and related compounds, revealing that 11 was an epimer of 1 at the C-5 position and 12 was a trithio-derivative of 11. The structures of 13-15 were established by analyzing their 1D and 2D NMR data. The absolute configurations of 13-15 were assigned by comparing their experimental electronic circular dichroism (ECD) spectra with the calculated ECD spectrum of 13.

Twenty-five limonoids from the Hainan mangrove, Xylocarpus granatum.

Twenty-four new limonoids (1-24), named hainanxylogranins A-X, were isolated from leaves and barks of the Hainan mangrove, Xylocarpus granatum, together with a known compound, tabulvelutin B (25). The structures of these compounds were established by high resolution electrospray ionization mass spectroscopy (HRESIMS), extensive NMR spectroscopic investigations, single-crystal X-ray diffraction analyses, and the comparison of experimental electronic circular dichroism (ECD) spectra. Most notably, the absolute configurations of seven compounds, viz., 1, 2, 6, 16, 17, 22, and 25, were unambiguously determined by single-crystal X-ray diffraction analyses, conducted with Cu Kα radiation. Compounds 1-4 belong to a unique group of mexicanolides containing a C3-O-C8 bridge and a C-17 substituted γ(21)-hydroxybutenolide moiety, whereas 5-9 are mexicanolides comprising a C1-O-C8 bridge. Compounds 10-16 are typical mexicanolides, among which 14 and 15 contain a C-17 substituted γ(23)-hydroxybutenolide moiety. Compounds 17 and 18 are phragmalin 8,9,30-orthoesters, whereas 19 and 20 are phragmalin 1,8,9-orthoesters. Compound 21 consists of a C1-O-C29 bridge, while 22-24 are derivatives of azadirone. The inhibitory activities of 1, 5-8, 11, 17, 19, 21-23, and 25 against human carboxylesterase 2 (CES2) were assayed. All the tested compounds exhibited inhibition rates of 30-64% at the concentration of 100.0µM.

Hyperacmosins H-J, three new polycyclic polyprenylated acylphloroglucinol derivatives from Hypericum acmosepalum

Three new polycyclic polyprenylated acylphloroglucinol derivatives, hyperacmosins H-J (1–3), with four known compounds (4–7), were isolated from the air-dried aerial parts of Hypericum acmosepalum. Especially, compounds 1 and 2 were identified as methylated polycyclic polyprenylated acylphloroglucinol derivatives (mPPAPs). Their structures were established by NMR, HRESIMS and experimental electronic circular dichroism (ECD) spectra. The hepatoprotective activity of seven compounds were evaluated. Compounds 1 and 5 exhibited hepatoprotective activity against paracetamol-induced HepG2 cell damage.

Terpenoids from the Deep-Sea-Derived Fungus Penicillium thomii YPGA3 and Their Bioactivities

A chemical study of the ethyl acetate (EtOAc) extract from the deep-sea-derived fungus Penicillium thomii YPGA3 led to the isolation of a new austalide meroterpenoid (1) and seven known analogues (2−8), two new labdane-type diterpenoids (9 and 10) and a known derivative (11). The structures of new compounds 1, 9, and 10 were determined by comprehensive analyses via nuclear magnetic resonance (NMR) and mass spectroscopy (MS) data. The absolute configurations of 1, 9, and 10 were determined by comparisons of experimental electronic circular dichroism (ECD) with the calculated ECD spectra. Compound 1 represented the third example of austalides bearing a hydroxyl group at C-5 instead of the conserved methoxy in other known analogues. To our knowledge, diterpenoids belonging to the labdane-type were discovered from species of Penicillium for the first time. Compound 1 showed cytotoxicity toward MDA-MB-468 cells with an IC50 value of 38.9 μM. Compounds 2 and 11 exhibited inhibition against α-glucosidase with IC50 values of 910 and 525 μM, respectively, being more active than the positive control acarbose (1.33 mM).

Theoretical study of the Raman optical activity spectra of with M=Co, Rh.

Vibrational Raman optical activity (ROA) spectra were calculated under off-resonance, near-resonance, and at-resonance conditions for (A) and under off-resonance conditions for (B) using a new driver software for calculating the ROA intensities from complex (damped) time-dependent linear response Kohn-Sham theory. The off-resonance spectra of A and B show many similarities. At an incident laser wavelength of 532nm, used in commercial ROA spectrometers, the spectrum of A is enhanced by near-resonance with the ligand-field transitions of the complex. The near-resonance spectrum exhibits many qualitative differences compared with the off-resonance case, but it remains bi-signate. Even under full resonance with the ligand-field electronic transitions, the ROA spectrum of A remains bi-signate when the electronic transitions are broadened such as to yield absorption line widths that are comparable with those in the experimental UV-vis absorption and electronic circular dichroism spectra.

Hyperacmosins E-G, three new homoadamantane-type polyprenylated acylphloroglucinols from Hypericum acmosepalum

Three new homoadamantane-type polyprenylated acylphloroglucinols, hyperacmosins E-G (1–3), with seven known compounds were isolated from the air-dried aerial parts of Hypericum asmosepalum. Their structures were determined by NMR, HRESIMS and experimental electronic circular dichroism (ECD) spectra. The hepatoprotective activity of these compounds were evaluated. Compounds 4 and 8 exhibited hepatoprotective activity against paracetamol-induced HepG2 cell damage.

Influencing the Self-Sorting Behavior of [2.2]Paracyclophane-Based Ligands by Introducing Isostructural Binding Motifs.

Two isostructural ligands with either nitrile (Lnit) or isonitrile (Liso) moieties directly connected to a [2.2]paracyclophane backbone with pseudo‐meta substitution pattern have been synthesized. The ligand itself (Lnit) or its precursors (Liso) were resolved by HPLC on a chiral stationary phase and the absolute configuration of the isolated enantiomers was assigned by XRD analysis and/or by comparison of quantum‐chemical simulated and experimental electronic circular dichroism (ECD) spectra. Surprisingly, the resulting metallosupramolecular aggregates formed in solution upon coordination of [(dppp)Pd(OTf)2] differ in their composition: whereas Lnit forms dinuclear complexes, Liso exclusively forms trinuclear ones. Furthermore, they also differ in their chiral self‐sorting behavior as (rac)‐Liso undergoes exclusive social self‐sorting leading to a heterochiral assembly, whereas (rac)‐Liso shows a twofold preference for the formation of homochiral complexes in a narcissistic self‐sorting manner as proven by ESI mass spectrometry and NMR spectroscopy. Interestingly, upon crystallization, these discrete aggregates undergo structural transformation to coordination polymers, as evidenced by single‐crystal X‐ray diffraction.

Trichothecenes from an Endophytic Fungus Alternaria sp. sb23.

Three new (alterchothecenes A - C, 1: -3: ) and 3 known (4: -6: ) trichothecenes, along with 9 known compounds (7: -15: ), were isolated from the culture of Alternaria sp. sb23, an endophytic fungus separated from the root of Schisandra sphenanthera Rehd. et Wils. Their structures were elucidated by spectroscopic analyses, and the absolute configurations of 1: -3: were determined through comparison of the experimental electronic circular dichroism (ECD) spectra and optical rotations with similar analogues. In vitro cytotoxicity tests of compounds 1: -6: against human HT-29 colon carcinoma and human MCF-7 breast cancer cell lines indicated that 4: -6: exhibited significant cytotoxic effects, with IC50 values ranging from 0.89 to 9.38 µM. And the potential of compounds 1: -6: as tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) sensitizers in HT-29 cells was evaluated. The results revealed that combination treatment of TRAIL with compounds 1: -6: synergistically decreased cell viability compared with the sole treatment with those compounds.

Cytotoxic and Anti-Inflammatory Effects of Ent-Kaurane Derivatives Isolated from the Alpine Plant Sideritis hyssopifolia.

This paper reports the isolation and structural characterization of four new ent-kaurane derivatives from the Lamiaceae plant Sideritis hyssopifolia. Planar structures and relative configurations were determined using both mass spectrometry and nuclear magnetic resonance (1D and 2D). Absolute configurations were determined by comparing experimental and theoretical electronic circular dichroism spectra. The cytotoxic and microbial activities of all new compounds were tested. Compounds that were non-cytotoxic were further evaluated for anti-inflammatory activity.

Circularly polarized luminescence of enantiopure carboline-based europium cryptates under visible light excitation

The enantiomers of carboline-based cryptates were successfully resolved by chiral HPLC. These complexes show high configurational stability under harsh conditions and their absolute configuration was determined by comparing theoretical and experimental electronic circular dichroism spectra. The enantiopure cryptates exhibit strong circularly polarized luminescence with a maximum dissymmetry factor glum = 0.25 for the f-f transition 5D0→7F1 (λ = 594 nm) under visible light excitation at λex = 400 nm.

Sesquiterpenoids from the aerial parts of Conyza japonica and their inhibitory activity against nitric oxide production

Four new sesquiterpenoids, conyterpenols A − D (1–4), along with nineteen known analogues (5–23) were isolated from the aerial parts of Conyza japonica. The structures of 1–4 were determined through spectroscopic analysis, while their absolute configurations were determined by comparison of calculated and experimental electronic circular dichroism (ECD) spectra. Conyterpenol D (4) was a new type of sesquiterpenoid with a seven-membered lactone ring. Compounds 1–23 were evaluated for their inhibitory activity against LPS-induced nitric oxide production in RAW264.7 macrophages and cytotoxicity against human hepatoma cell line (HepG2) and human breast adenocarcinoma cell line (MCF-7). Compounds 3, 4, and 12 displayed moderate inhibition against NO production with IC50 values in the range of 26.4–33.6 μM. And all compounds showed no obvious cytotoxicity against these two cancer cell lines at 100 μM.