ECD Data Research Articles

Phenylpropanoid amides from Solanum rostratum and their phytotoxic activities against Arabidopsis thaliana.

Solanum rostratum, an annual malignant weed, has seriously damaged the ecological environment and biodiversity of invasion area. This alien plant gains a competitive advantage by producing some new phytotoxic substances to inhibit the growth of native plants, thus achieving successful invasion. However, the chemical structures, inhibitory functions and action mechanisms of phytotoxic substances of S. rostratum remain unclear. In this study, to clarify the chemical structures of phytotoxic substances from S. rostratum, we isolated phenylpropanoid amides from the plant. Their structures were identified by comprehensive HR-ESIMS, NMR and ECD data. And the inhibitory functions of isolated phenylpropanoid amides on one model plant (Arabidopsis thaliana) were also investigated. In addition, the action mechanisms of active phenylpropanoid amides were revealed by antioxidant-related enzymes [Catalase (CAT), Peroxidase (POD), Superoxide dismutase (SOD)] activities and corresponding molecular docking analyses. Phytochemical research on the whole plant of S. rostratum led to the isolation and identification of four new phenylpropanoid amides (1-4), together with two known analogues (5-6). All the compounds showed phytotoxic effects with varying levels on the seed germination and root elongation of one model plant (Arabidopsis thaliana), especially compound 2 and 4. Likewise, compounds 2 and 4 displayed potent inhibitory effects on antioxidant-related enzyme (POD). In addition, compounds 2 and 4 formed common conventional hydrogen bonds with residues Ala34 and Ser35 in POD revealed by molecular docking analyses. These findings not only helped to reveal the invasion mechanism of S. rostratum from the perspective of "novel weapons hypothesis", but also opened up new ways for the exploitation and utilization of S. rostratum.

Discovery of Bioactive Metabolites by Acidic Stress to a Geldanamycin Producer, Streptomyces samsunensis.

In an effort to activate silent biosynthetic gene clusters, Streptomyces samsunensis DSM42010, a producer of geldanamycin, was cultured at four different pHs (4.5, 5.4, 6.6, and 7.4). An acidic culture condition (pH 5.4) was selected for a chemical investigation since S. samsunensis showed a different metabolic profile compared to when it was cultured under other conditions. Seven new (1-7) and four known (8-11) compounds were isolated from these cultures. The structures of the isolated compounds were determined by spectroscopic techniques and chemical derivatization. Relative and absolute configurations of the new compounds (1-5) were established using JBCA, PGME method, advanced Marfey's method, modified Mosher's method, and comparison of observed and calculated ECD data. Interestingly, compounds 1-3 were truncated versions of geldanamycin, and compound 4 was also deduced to originate from geldanamycin. Compound 5 was composed of 3-methyltyrosine and 6-hydroxy-2,4-hexadienoic acid connected through an amide bond. Compounds 6 and 7 were dihydrogenated forms of geldanamycin with a hydroxy substitution. It is possible that culturing this strain under acidic conditions interfered to some degree with the geldanamycin polyketide synthase, leading to production of truncated versions as well as analogues of geldanamycin. Compounds 1, 8, and 9 showed significant antivirulence activity, inhibiting production of α-toxin by methicillin-resistant Staphylococcus aureus without growth attenuation and global regulatory inhibition; compounds 1, 8, and 9 may become promising α-toxin-specific antivirulence leads with less risk of resistance development.

Two pairs of new isobenzofuranone enantiomers from a soil-derived fungus Penicillium canescens DWS225

Two pairs of new isobenzofuranone derivative enantiomers, (±)-penicifurans E (1) and (±)-penicifurans F (2), together with four know compounds (3–6) were isolated from the solid fermentation of Penicillium canescens DWS225. The structures of these enantiomers were elucidated by extensive NMR spectroscopic data, and their absolute configurations were assigned by the experimental and calculated ECD data. The neuroprotective effects of all the isolates against oxygen-glucose deprivation/reperfusion injury in pheochromocytoma-12 cells (PC12) were investigated.

Meliasendanins E-J, Nor-neolignan Constituents from Melia toosendan and their Anti-inflammatory Activity

A phytochemical investigation of the fruits extract of Melia toosendan afforded the isolation of two new nor-neolignans, meliasendanins E (1) and F (2), as well as twelve known compounds (3 - 14) using various separation technique such as Diaion HP20, silica, RP-18 gel column chromatography and semi-preparative HPLC. Their chemical structures were elucidated by extensive NMR spectroscopic data including 2D-NMR, and HR-ESI-MS as well as ECD data. Among the twelve known compounds, the absolute structures of 3 - 6 were determined first, and given the trivial names as meliasendanins G-J (3 - 6). Based on the evaluation of anti-inflammatory activity, compounds 7 - 8 exhibited inhibitory effects on LPS-induced nitric oxide production in RAW 264.7 macrophages with IC50 values of 34.6 and 39.5 μM, respectively.

Guaianolides from Achillea millefolium L. and their anti-inflammatory activity

Seven previously undescribed guaianolides, millefolactons A–G, and three known analogues, millefoliumins A–C, were isolated from the whole plant of Achillea millefolium L. growing in Xinjiang, China. Their structures were elucidated using the HR-ESI-MS and NMR data analyses. The absolute configurations of millefolactons A–G were determined by single-crystal X-ray crystallography, ECD data analysis, and quantum-chemical ECD calculations. Millefolactons A–E are rare 3-oxa-guaianolides. Millefolacton C, millefolacton E, millefoliumin A and millefoliumin B exhibited enzymatic inhibition of 15-LOX. Molecular docking simulations were conducted to visualize interactions between the four active compounds and 15-LOX and determine binding mechanisms. Moreover, a LPS-induced BV2 cell model was used to further investigate the anti-inflammatory mechanism of millefolacton C. As a result, millefolacton C significantly inhibited NO release, repressed levels of pro-inflammatory cytokines including TNF-α, IL-18, PGE2 and IL-6, and inhibited the protein expression of iNOS and COX2 proteins. In addition, millefolacton C could potently decreased the expression of NLRP3, ASC, and IL-1β proteins in LPS-stimulated BV2 cells. These results indicate that the 3-oxa-guaianolides from A. millefolium L. offer great potential as leads for anti-inflammatory drug development.

Insights into the Structures of Bilirubin and Biliverdin from Vibrational and Electronic Circular Dichroism: History and Perspectives.

In this work we review research activities on a few of the most relevant structural aspects of bilirubin (BR) and biliverdin (BV). Special attention is paid to the exocyclic C=C bonds being in mostly Z rather than E configurations, and to the overall conformation being essentially different for BR and BV due to the presence or absence of the double C=C bond at C-10. In both cases, racemic mixtures of each compound of either M or P configuration are present in achiral solutions; however, imbalance between the two configurations may be easily achieved. In particular, results based on chiroptical spectroscopies, both electronic and vibrational circular dichroism (ECD and VCD) methods, are presented for chirally derivatized BR and BV molecules. Finally, we review deracemization experiments monitored with ECD data from our lab for BR in the presence of serum albumin and anesthetic compounds.

Prenylated dihydroflavones from the root barks of Morus alba

Three new prenylated dihydroflavones, moralbaflavones A–C (1–3), together with four known ones (4a/4b, 5, and 6) were isolated from the root barks of Morus alba L. Their structures including the absolute configurations were determined by the analysis of HRMS, NMR, and ECD data. The neuroprotective properties of these prenylated dihydroflavones were screened at the concentration of 10 µM in the sodium nitroprusside-induced rat pheochromocytoma PC-12 cells, and the results showed moralbaflavone C (3) possessed significant neuroprotective activity, being more potent than the positive control edaravone.

Two New Enantiomers of Phenylethanoid and Their Anti-Inflammatory Activities.

In this phytochemical investigation, two pairs of new phenylethanoid derivative enantiomers (1a/1b and 2a/2b), a new phenylethanoid derivative 3b, and seven known compounds (3a, 4-9) were isolated from the leaves of Picrasma quassioides. Spectroscopic techniques were used for the elucidation of their chemical structures, and the absolute configurations were determined by a comparison between the experimental and calculated ECD data, as well as the application of Snatzke's method. Compounds (1a/1b-3a/3b) were measured for their production of NO levels in LPS-induced BV-2 microglial cells. The results showed that all compounds exhibited potential inhibitory effects, and compound 1a showed stronger activity than the positive control.

Jiangchuanmycin, a New Pyrrolizidine Analog from Streptomyces sp. YIM S01863.

Jiangchuanmycin (1), a new indole containing pyrrolizidine, and six known peptides (2-7) were obtained from the fermentation broth of a Streptomyces isolate collected from a sediment sample of Xingyun Lake, Jiangchuan, China. Their structures were elucidated on the detailed analysis of the HR-ESI-MS, 1D and 2D NMR, ECD, and X-ray crystallographic data. Jiangchuanmycin (1) presented weak inhibitory effects on cell lines of H1299, MHCC97H, HCT116 with the IC50 values of 97.6 μM, 98.6 μM and 40.6 μM, respectively.

Garcowacinols A-J, cytotoxic polyprenylated benzoylphloroglucinol derivatives from the twigs of Garcinia cowa

Ten undescribed polyprenylated benzoylphloroglucinol derivatives named garcowacinols A‒J (1–10) and four known analogues (11–14) were isolated from the twigs of Garcinia cowa. Their structures were determined by spectroscopic data analysis (1D and 2D NMR and HRESIMS), and their absolute configurations were established based on NOESY and ECD data. All isolated compounds were evaluated for their cytotoxicity against five types of human cancer cells (KB, HeLa S3, MCF-7, Hep G2, and HT-29) as well as Vero cells by MTT colorimetric assay. Garcowacinol C was significantly active against all the five cancer cells with IC50 values in the range of 0.61–9.50 μM. Selective proliferative inhibitions were observed on garcowacinol F and 7-epiclusianone against KB cells, and guttiferone Q toward MCF-7 cells with IC50 values less than 10 μM.

2,3-Dihydrosorbicillin and chrysopanol stimulate insulin secretion in INS-1 cells

Pancreatic β-cell function and insulin secretion are important in antidiabetic drug development. In an effort to discover small molecules to regulate insulin secretion, an endophytic fungus, Penicillium sp. SSP-1CLG, was selected for chemical investigation. Large scale cultures of the strain followed by extraction and chromatographic analysis led to the isolation of 10 anthraquinone and alkaloid-type compounds. The isolated compounds were identified by comprehensive analysis of NMR, MS, and ECD data. The effect of compounds 1–10 on insulin secretion in INS-1 cells was investigated. 2,3-Dihydrosorbicillin (1), chrysophanol (2), and glandicolin B (10) at non-cytotoxic concentrations resulted in an increase of glucose-stimulated insulin secretion (GSIS) in rat INS-1 pancreatic β-cells. Furthermore, we investigated the signaling pathway involved in 2,3-dihydrosorbicillin (1) and chrysophanol (2) action in the activation of peroxisome proliferator-activated receptor γ (PPARγ), pancreatic and duodenal homeobox-1 (PDX-1), insulin receptor substrate-2 (IRS-2), phosphatidylinositol 3-kinase (PI3K), and Akt. Treatment of INS-1 cells with 2,3-dihydrosorbicillin (1) and chrysophanol (2) increased the expression of these proteins. Our findings indicate that 2,3-dihydrosorbicillin and chrysophanol may play roles in the regulation of insulin secretion in pancreatic β-cells, at least in part, by targeting PPARγ and PDX-1 via the IRS-2/PI3K/Akt signaling pathway.

Two new alkaloids from the endophytic fungus Schizophyllum sp. HM230 isolated from Vincetoxicum mongolicum Maxim

Endophytic fungi is an important source for the discovery of bioactive natural compounds. A chemical investigation of the ethyl acetate extract of the endophytic fungus Schizophyllum sp. HM230 derived from stems of the herb Vincetoxicum mongolicum Maxim led to isolation of five alkaloids, including two new compounds, schizophyllins M (1) and N (2), along with three known ones (3–5). The planar structures of two new compounds were elucidated by extensive spectroscopic methods including MS, 1D and 2D NMR. Their absolute configurations were determined by Mosher’s method and comparison of the ECD data. All the isolates were evaluated for their cytotoxicity and antioxidant activities. Compounds 1–4 showed middle cytotoxicity against MCF-7 cells with IC50 values range of 68.1 ∼ 87.32 μM. Compounds 1–5 displayed obvious antioxidant activity with the IC50 values range of 0.86 ∼ 5.78 mg/mL.

Gastroprotective 2-(2-phenylethyl)chromone-sesquiterpene hybrids from the resinous wood of Aquilaria sinensis (Lour.) Gilg

Six previously unprecedented 2-(2-phenylethyl)chromone-sesquiterpene hybrids, aquisinenins A–F (1 – 6), were isolated from the resinous wood of Aquilaria sinensis by a LC-MS-guided fractionation procedure. Their structures were determined by extensive spectroscopic analysis (1D and 2D NMR, UV, IR, and HRMS) and experimental and computed ECD data. Compounds 1 – 6 were rare dimeric 2-(2-phenylethyl)chromone-sesquiterpene derivatives featuring 5,6,7,8-tetrahydro-2-(2-phenylethyl)chromone hybridized with different sesquiterpene (eudesmane/guaiane type) moieties via ester bond. Furthermore, all the isolated compounds were evaluated for their protective effects on taurocholic acid (TCA)-induced GES-1 cell injury. The most effective aquisinenin F (6) was used to elucidate the involved mechanism on protection against TCA-induced gastric mucosal damage. Our results indicated that 6 protected against gastric mucosal cell insult by downregulation of the ER stress triggered by TCA.

Diversity of sesquiterpenoids from Stellera chamaejasme with neuroprotective effects

Chromatographic fractionation of the 95% EtOH extract of the roots of Stellera chamaejasme yielded 20 sesquiterpenoids of four different types, guaiane-, carotane-, sesquicarane-, and alpiniane-types. Among them, sesquistrachanoids A−F were previously undescribed ones, whose structures including absolute configurations were elucidated by spectroscopic methods, the Mo2(OAc)4-induced ECD experiment, and analysis of experimental and calculated 1D NMR and ECD data. Sesquistrachanoid A is a 2,3-seco-guaiane-type sesquiterpenoid with a α-pyrone core and sesquistrachanoid B is the first example of 8,9-seco-guaiane-type sesquiterpenoid featured with an 1,8-δ-lactone core. Sesquistrachanoid C is a guaiane sesquiterpenoid characterized by a peroxide bridge between C-8 and C-10. All sesquiterpenoids were evaluated for their neuroprotective effects on cell damage induced by sodium nitroprusside in PC-12 cells. The bioassay results showed that six compounds at 10 μM could restore the cell viability, being comparable to that of the positive control edaravone. The mechanistic study on the most pronounced activity compound, stelleraguaianone B, demonstrated that it played a neuroprotective role by promoting the mRNA expression of antioxidant enzymes to reduce oxidative stress.

Thorectidiol A Isolated from the Marine Sponge Dactylospongia elegans Disrupts Interactions of the SARS-CoV-2 Spike Receptor Binding Domain with the Host ACE2 Receptor.

Thorectidiols isolated from the marine sponge Dactylospongia elegans (family Thorectidae, order Dictyoceratida) collected in Papua New Guinea are a family of symmetrical and unsymmetrical dimeric biphenyl meroterpenoid stereoisomers presumed to be products of oxidative phenol coupling of a co-occurring racemic monomer, thorectidol (3). One member of the family, thorectidiol A (1), has been isolated in its natural form, and its structure has been elucidated by analysis of NMR, MS, and ECD data. Acetylation of the sponge extract facilitated isolation of additional thorectidiol diacetate stereoisomers and the isolation of the racemic monomer thorectidol acetate (6). Racemic thorectidiol A (1) showed selective inhibition of the SARS-CoV-2 spike receptor binding domain (RBD) interaction with the host ACE2 receptor with an IC50 = 1.0 ± 0.7 μM.

In Vitro Hypoglycemic Diterpenoids from the Roots of Croton yunnanensis.

Fifteen compounds including nine new diterpenes were isolated from the roots of Croton yunnanensis. By HRESIMS, NMR, ECD data, and X-ray diffraction analysis, the new compounds were characterized as eight neo-clerodane diterpenes (compounds 1-8) and one 15,16-dinor-ent-pimarane diterpene (9). All diterpenes were assayed for their hypoglycemic activities. Compounds 1-4, 6, 7, and 10 promoted glucose uptake activity in insulin-resistant 3T3-L1 adipocytes. Compounds 1 and 6 showed insulin sensitizing activity, potentiating conspicuously their glucose uptake activity at a concentration of 20 μM when treated synergistically with low-concentration insulin at 1 nM.

Oudemansin and 9-methoxystrobilurin derivatives with antimalarial activity from cultures of the basidiomycete Favolaschia minutissima: assignments of the absolute configurations of the isoprene-derived units.

Five undescribed polyketide metabolites, oudemansins E (1), M (2), P (3), and Q (4), and 9-methoxystrobilurin I (5), were isolated from cultures of basidiomycete Favolaschia minutissima TBRC-BCC 19434. A γ-lactone derivative (6) of noroudemansin A (8), which was previously reported as a semisynthetic compound, was also isolated. The absolute configuration of the isoprene-derived moiety of the known cometabolite 9-methoxystrobilurin E (9) was determined to be 2'R,6'S by comparison of the experimental and calculated ECD data, which was correlated to the new derivative 1. These compounds exhibited antimalarial activity against Plasmodium falciparum K1 (multidrug-resistant strain). A putative minor natural product, namely 9-methoxystrobilurin P (13), was prepared by semisynthesis, which exhibited significant antimalarial activity (IC50 0.086 μM).

New alkaloids from Polygonatum zanlanscianense Pamp

Sixteen alkaloid compounds were isolated from the dried rhizomes of P. zanlanscianense, including a pair of new enantiomers (R/S)-7'-ethoxy-trans-p-couma-royltyramine (1a/1b) and 14 known compounds (2-14) isolated from this plant for the first time. The structures of new compounds were identified by IR, NMR and MS spectroscopic analysis, and their absolute configurations were determined by comparison of the experimental and calculated ECD data.

Anonazepine, a new alkaloid from the leaves of Annona muricata (Annonaceae).

From the CHCl3-soluble extract of Annona muricata L. (Annonaceae) leaves, one new 3-benzazepine-type alkaloid, anonazepine (1), and four known aporphine-type alkaloids, (+)-laurotetanine (2), (+)-norglaucine (3), (-)-xylopine (4), and lanuginosine (5), were isolated. Except for (-)-xylopine (4), these remaining known alkaloids were first reported in A.muricata. The structures of the isolated alkaloids were established by 1D and 2D NMR spectroscopy and MS, as well as comparison with literature data. Thenew3-benzazepine-type alkaloid existed in an inseparable mixture of two equilibrium conformers. Its absolute configuration was determined based on comparingtheirexperimental and calculated ECD data. Theanti-inflammatory activity of the isolated alkaloids was investigated, but none of the alkaloids showed a significant result.

Structural elucidation of two new polypropionates from the marine slug Paromoionchis tumidus by spectroscopic analyses and DFT calculations

Tumiduspyrones A and B (1‒2), two new C17 and C18 polypropionates, and three known compounds (3‒5) were isolated from the sea slug Paromoionchis tumidus. Their structures and the absolute configurations of 1 and 2 were elucidated by spectroscopic analyses and quantum chemical calculations of the ECD and NMR data. The stereochemistry of compound 1 was also established based on the single-crystal X-ray diffraction method. In antimicrobial assays, only (E)-4-(1H-indol-3-yl)but‑3-en-2-one (3) showed moderate activity, whereas remaining compounds were weakly active.