α-Glucosidase inhibitory and nitric oxide production inhibitory activities of alkaloids isolated from a twig extract of Polyalthia cinnamomea

The first phytochemical investigation of Polyalthia cinnamomea led to the isolation and identification of two new oxoprotoberberine alkaloids, (−)-(13aS)-polyalthiacinnamines A and B, together with eleven known compounds. The structures of the new compounds were elucidated by extensive spectroscopic methods. The absolute configuration of miliusacunine E and consanguine B was established by X-ray diffraction analysis using Cu Kα radiation and ECD spectra, whereas the absolute configurations of polyalthiacinnamines A and B were established by comparison of their ECD spectra and specific rotations with those of miliusacunine E and consanguine B. Compounds 1–4, 6, and 8 exhibited α-glucosidase inhibitory activities (IC₅₀ values ranging from 11.3 to 57.9 µM) better than a positive control (acarbose, IC₅₀ 83.5 μM). Compound 2 also exhibited NO production inhibitory activity with an IC₅₀ value of 24.4 μM (indomethacin, a positive control, IC₅₀ = 32.2 μM).     

Bioactive terpenoids from Silybum marianum and their suppression on NO release in LPS-induced BV-2 cells and interaction with iNOS

Three new (1–3) and one known (4) bioactive terpenoids were isolated from the seeds of Silybum marianum based on the investigation to get new NO inhibitors. Their structures were determined by extensive NMR (1D and 2D NMR) and MS spectroscopic data, and the absolute configurations were identified by experimental and calculated ECD spectra. The NO inhibitory activities in murine microglial BV-2 cells and interactions with iNOS protein by molecular docking were evaluated for all compounds. The results showed that these compounds had potent NO inhibitory effects.     

Three new flavonoids from Millettia pachyloba

Two new prenylated isoflavones, pachyloisoflavone A (1), pachyloisoflavone B (2), and a new pterocarpan, pachylobin A (3), together with ten known flavonoids (4–13), were isolated from the vine stems and leaves of Millettia pachyloba. The structures of new compounds were elucidated on the basis of extensive spectroscopic data interpretation, including 1D, 2D NMR and HREIMS. The absolute configuration of 2 was established by the comparison of experimental and calculated electronic circular dichroism (ECD) spectra.     

Unusual cadinane-type sesquiterpene glycosides with α-glucosidase inhibitory activities from the fruit of Cornus officinalis Sieb. et Zuuc.

Five novel and rare cadinane-type sesquiterpene glycosides, cornucadinoside A-E (1–5) were isolated from water extract of the fruit of Cornus officinalis Sieb. et Zuuc.. The new chemical structures, together with their absolute configurations, were elucidated on the basis of extensive spectroscopic analysis, including a comparison of their experimental and calculated electronic circular dichroism (ECD) spectra. Their structures, which possess a naphthalene skeleton, are the first report on the occurrence of cadinane sesquiterpene glycosides in Cornus. Additionally, all the compounds exhibited marked α-glucosidase inhibitory activity except for 3 in vitro.     

Unusual CD couplet pattern observed for the pi*<--n transition of enantiopure (Z)-8-methoxy-4-cyclooctenone: an experimental and theoretical study by electronic and vibrational circular dichroism spectroscopy and density functional theory calculation

Ultraviolet absorption (UV) and electronic circular dichroism (ECD) spectra of enantiopure (Z)-8-methoxy-4-cyclooctenone (MCO) were measured in hexane to give a normal single UV absorption band at 298 nm, which is assigned to the carbonyl's pi*<--n transition. Unexpectedly, the ECD spectrum exhibited an apparent couplet pattern with vibrational fine structures. Obviously, the conventional CD exciton coupling mechanism cannot be applied to this bisignate CD signal observed for single-chromophoric MCO. Variable temperature-ECD and vibrational circular dichroism (VCD) spectral measurements, simultaneous UV and ECD spectral band resolution, and density functional theory (DFT) calculations of energy and structure revealed that this apparent CD couplet originates from a rather complicated spectral overlap of more than three conformers of MCO, two of which exhibit mirror-imaged ECD spectra at appreciably deviated wavelengths. In the simultaneous band-resolution analysis, the observed UV and ECD spectra were best fitted to four overlapping bands. Two major conformers were identified by comparing the experimental IR and VCD spectra with the simulated ones, and the other two by comparing the observed UV and ECD spectra with the theoretical ones obtained by time-dependent DFT calculations. It was shown that the combined use of experimental ECD and VCD spectra and theoretical DFT calculations can give a reasonable interpretation for the Cotton effects of the conformationally flexible molecule MCO.     

Eryloside W,a triterpenoid saponin from the sponge Dictyonella marsilii

A new saponin derivative named eryloside W was isolated from the marine sponge Dictyonella marsilii (Demospongiae, Halichondrida, Dictyonellidae). The structure of the compound was elucidated through extensive use of 1D and 2D nuclear magnetic resonance and mass spectrometry. Determination of the absolute configuration was performed using electronic circular dichroism (ECD) by comparison of experimental and time dependent density functional theory (TDDFT) calculated spectra. This is the first occurrence of a saponin derivative produced by a marine sponge present in the Mediterranean.     

Natural NO inhibitors from the leaves of Callicarpa kwangtungensis: Structures,activities, and interactions with iNOS

A phytochemical investigation to obtain new NO inhibitors resulted in the isolation of a new diterpenoid with a rare 9,10-seco-abietane skeleton (1) and twelve known terpenoids (2–13) from Callicarpa kwangtungensis. Their structures were elucidated on the basis of extensive 1D and 2D NMR spectroscopic data analyses, and the absolute configuration of compound 1 was established by comparison of the calculated and experimental electronic circular dichroism (ECD) spectra. The inhibitory activities on lipopolysaccharide-induced NO production in murine microglial BV-2 cells of these terpenoids were evaluated, and all of the compounds showed inhibitory effects. The following molecular docking studies showed interactions of the bioactive compounds with the iNOS protein.     

A new acorane sesquiterpenes of Lysionotus pauciflorus maxim. Form Guizhou province,China

A new acorane sesquiterpene (1), together with fourteen known compounds were isolated from the whole plant of Lysionotus pauciflorus Maxim. The chemical structures of the compounds were identified by physio-chemical properties and 1D-NMR, 2D-NMR, ESI-MS, IR and ECD spectra. Among them, six compounds (1, 4, 6, 7, 13, 15) were first found in the genus Lysionotus. The chemotaxonomic significance of the isolated compounds in the genus Lysionotus and family Gesneriaceae were discussed.     

Trichocarotins A–H and trichocadinin A,nine sesquiterpenes from the marine-alga-epiphytic fungus Trichoderma virens

In addition to CAF-603, 14-hydroxy CAF-603 (trichocarane B), 7-β-hydroxy CAF-603, and trichocarane A, eight new carotane sesquiterpenes, trichocarotins A–H, and one new cadinane sesquiterpene, trichocadinin A, were isolated from the culture of Trichoderma virens Y13-3, obtained from the surface of a marine red alga. Their structures and relative configurations were unambiguously assigned by interpretation of 1D/2D NMR and MS data, and their absolute configurations were established by X-ray diffraction or ECD spectra aided by quantum chemical calculations. These compounds represent two rarely occurring sesquiterpene types from filamentous fungi, and six of them feature potent inhibition against some marine plankton species.     

Electronic Circular Dichroism of Chiral Alkenes: B3LYP and CAM‐B3LYP Calculations

Time‐dependent density functional theory (TDDFT) calculations of electronic circular dichroism (ECD) are widely used to determine absolute configurations (ACs) of chiral molecules. Two very popular DFT exchange‐correlation functionals, one hybrid (B3LYP) and one long‐range corrected (CAM‐B3LYP), along with a hierarchical sequence of basis sets were investigated, and the ECD spectra predicted for eight alkenes and compared to gas‐phase experimental spectra. Little variation in predicted ECD spectra was found with the basis set size enlargement, but the sensitivity to the functional is greater. Good agreement was obtained only with the CAM‐B3LYP functional, leading to the conclusion that TDDFT calculations of ECD spectra can routinely provide reliable ACs if and only if an appropriate functional is used. For camphene, twistene, syn‐(E)‐bisfenchylidene, and phyllocladene, solvent effects were estimated. Chirality 27:23–31, 2015. © 2014 Wiley Periodicals, Inc.     

Sesquiterpenoids and steroids from gorgonian Echinogorgia sassapo reticulate

Three guaiane-type sesquiterpenoids (1−3) and five steroids with 3β-hydroxy-5-en-7-one moiety (4−8) were obtained from gorgonian Echinogorgia sassapo reticulata collected from the South China Sea. Among them, new compound 1 was identified as (1S,5S,8S)-8-methoxy-menelloide B by spectroscopic methods including IR, HRESIMS, 1D and 2D NMR, and ECD spectra. All compounds except for 3 were obtained for the first time from the genus Echinogorgia. The chemotaxonomic significance of these compounds was summarized.     

Piperhancosides A−C,new lignan glycosides from the stems of Piper hancei Maxim

Three new lignan glycosides, piperhancosides A−C (1−3), and two known compounds (4−5) were isolated from the n-BuOH extract of the stems of Piper hancei Maxim. The planar structures of the new compounds were elucidated by extensive spectroscopic analyses. Their relative and absolute configurations were determined by coupling constants, chemical shift differences, acid hydrolysis, enzymatic hydrolysis, and experimental ECD spectra. All the isolates were evaluated for their antineuroinflammatory and antioxidant activities, and compounds 4 and 5 showed significant DPPH.+ radical scavenging ability with EC₅₀ value of 14.07 and 16.48 μM, respectively.     

Rapid isolation and identification of minor natural products by LC–MS,LC–SPE–NMR and ECD: Isoflavanones,biflavanones and bisdihydrocoumarins from Ormocarpum kirkii

The combination of the hyphenated techniques LC–MS and LC–SPE–NMR constitutes a powerful platform for the rapid isolation and identification of minor components from natural sources. Electronic circular dichroism (ECD) is a useful tool to determine the absolute configuration of small quantities of chiral molecules. In order to search for minor constituents present in an Ormocarpum kirkii extract, these techniques were applied for the separation and structure elucidation of a series of isoflavanones, biflavanones and biscoumarins. After optimization of chromatographic conditions and subsequent isolation, MS and 1D and 2D NMR data were collected. Experimental and calculated ECD spectra were used in conjunction with NMR data to confirm the absolute configuration of these compounds. Eight compounds were identified for the first time and six have been previously reported. The present approach offers a strategy for accelerating research on natural products.     

De novo peptide sequencing using CID and HCD spectra pairs

In tandem mass spectrometry (MS/MS), there are several different fragmentation techniques possible, including, collision‐induced dissociation (CID) higher energy collisional dissociation (HCD), electron‐capture dissociation (ECD), and electron transfer dissociation (ETD). When using pairs of spectra for de novo peptide sequencing, the most popular methods are designed for CID (or HCD) and ECD (or ETD) spectra because of the complementarity between them. Less attention has been paid to the use of CID and HCD spectra pairs. In this study, a new de novo peptide sequencing method is proposed for these spectra pairs. This method includes a CID and HCD spectra merging criterion and a parent mass correction step, along with improvements to our previously proposed algorithm for sequencing merged spectra. Three pairs of spectral datasets were used to investigate and compare the performance of the proposed method with other existing methods designed for single spectrum (HCD or CID) sequencing. Experimental results showed that full‐length peptide sequencing accuracy was increased significantly by using spectra pairs in the proposed method, with the highest accuracy reaching 81.31%.     

Phytochemicals with NO inhibitory effects and interactions with iNOS protein from Trigonostemon howii

A phytochemical investigation to obtain new NO inhibitors led to the isolation of nine compounds including one new guaiane-type sesquiterpenoid (1) and two new cleistanthane diterpenoids (2 and 3) from the stems of Trigonostemon howii. Their structures were elucidated on the basis of extensive 1D and 2D NMR spectroscopic data analysis, and the absolute configurations of new compounds 1–3 were established via comparison of experimental and calculated electronic circular dichroism (ECD) spectra. Compounds 2 and 3 possess a rare 3,4-seco-cleistanthane diterpenoid skeleton. All of the compounds showed inhibitory effects on lipopolysaccharide-induced NO production in murine microglial BV-2 cells. The further molecular docking studies indicated the strong interactions between some bioactive compounds with the iNOS protein, which revealed the possible and potential mechanism of NO inhibition of bioactive compounds.     

Determination of absolute configuration and binding efficacy of benzimidazole-based FabI inhibitors through the support of electronic circular dichroism and MM-GBSA techniques

We have previously reported benzimidazole-based compounds to be potent inhibitors of FabI for Francisella tularensis (FtFabI), making them promising antimicrobial hits. Optically active enantiomers exhibit markedly differing affinities toward FtFabI. The IC₅₀ of benzimidazole (?)-1 is ～100× lower than the (+)-enantiomer, with similar results for the 2 enantiomers. Determining the absolute configuration for these optical compounds and elucidating their binding modes is important for further design. Electronic circular dichroism (ECD) quantum calculations have become important in determining absolute configurations of optical compounds. We determined the absolute configuration of (?)/(+)-1 and (?)/(+)-2 by comparing experimental spectra and theoretical density functional theory (DFT) simulations of ECD spectra at the B3LYP/6-311+G(2d, p) level using Gaussian09. Comparison of experimental and calculated ECD spectra indicates that the S configuration corresponds to the (?)-rotation for both compounds 1 and 2, while the R configuration corresponds to the (+)-rotation. Further, molecular dynamics simulations and MM-GBSA binding energy calculations for these two pairs of enantiomers with FtFabI show much tighter binding MM-GBSA free energies for S-1 and S-2 than for their enantiomers, R-1 and R-2, consistent with the S configuration being the more active one, and with the ECD determination of the S configuration corresponding to (?) and the R configuration corresponding to (+). Thus, our computational studies allow us to assign (?) to (S)- and (+) to (R)- for compounds 1 and 2, and to further evaluate structural changes to improve efficacy.     

Bisabololoxide derivatives from Artemisia persica,and determination of their absolute configurations by ECD

Five antiplasmodial bisabololoxide sesquiterpene diesters were isolated from an EtOAc extract of the aerial parts of Artemisia persica following an HPLC-time-based activity profiling of the extract. Structure elucidation was achieved by 1D and 2D NMR experiments. Relative configurations of cyclohexenone/cyclohexene and tetrahydropyran moieties of 1–5 were established on the basis of ³J_H–H coupling constants and NOE difference spectra. Stereochemical correlation of the two rings, and assignment of absolute configuration of 1–5 were achieved by comparison of experimental ECD spectra with simulated ECD data for possible stereoisomers, by using time dependent density function theory (TDDFT). Bisaboloids 1–4 exhibited in vitro antimalarial activity against Plasmodium falciparum, with IC₅₀ values ranging from 2.8 to 20.1 μM, and selectivity indices (SI) in L-6 cells of 3.7–11.9.     

Structures and biological activities of brominated azaphilones produced by Penicillium sclerotiorum E23Y–1A

Two new brominated azaphilones, 5-bromoisorotiorin (1) and penicilazaphilones H (2), along with a known azaphilone, 5-bromosclerotiorin (3) were isolated from the marine-derived fungus Penicillium sclerotiorum E23Y–1A cultivated on the solid rice medium with 3.3%NaBr. The structures of three compounds were elucidated based on 1D and 2D NMR spectra as well as HRESIMS data. Their absolute configurations were determined by ECD spectra analysis. Compounds 1-3 showed moderate antibacterial activities against Staphylococcus aureus ATCC 25923 with diameter of the inhibition zones of 8.08 ± 0.01, 7.50 ± 0.05 and 8.17 ± 0.05 mm, respectively, as well as compound 3 exhibited weak inhibitory activity against AChE.     

Absolute configuration determination of isoflavan-4-ol stereoisomers

Elucidation of the correct stereochemistry of the metabolite is essential for the mechanistic study of bioactive compounds. Isoflavan-4-ol has the same chiropical chromophore as THD, the biosynthetic precursor of the potent phytoestrogen S-equol. Interested in the correct absolute configuration of isoflavan-4-ol stereoisomers and to compare the available practical approaches for the absolute configuration determination, complete absolute configuration analysis of isoflavan-4-ol stereoisomers has been carried out with by means of ECD and VCD spectroscopy as well as modified Mosher method. Theoretical TD-DFT computations resulted in a poor simulation of the observed experimental ECD spectra, and thus inconclusive absolute configuration assignments of isoflavan-4-ol stereoisomers were obtained. However, DFT-assisted VCD spectroscopic analyses successfully determined correct absolute configurations, and further confirmed by modified Mosher method.     

Cytotoxic oligophenols from the rhizome of Wikstroemia indica

A new tricoumarin glycoside, triumbelletin-7-O-β-d-glucoside (1) and a new biflavonoid, wikstroflavone A (2), together with two known compounds, wikstaiwanone A (3) and wikstaiwanone B (4), were isolated from the rhizome of Wikstroemia indica. The structures of new compounds were elucidated by extensive spectroscopic techniques (UV, IR, HRESIMS, 1D, 2D NMR and CD), in combination with quantum chemical calculations of ¹³C NMR and ECD spectra. All isolates were tested for their antineoplastic activities against cancer-derived cell lines HCT116, SW480, U87 and T98G. Compounds 2–4 exhibited moderate cytotoxic activities to the four cell lines. The flow cytometry assay and western blot analysis revealed that the cytotoxic effects were possibly attributed to the induced apoptotic cell death.