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Background: Spider venom show abundant diversity in both peptides and proteins, which play essential roles in new drug development and agrochemistry. The venoms of Macrothele yani species have strong toxicity on the victims. Objective: The purpose of this study is to comprehensively characterize the profile of venom proteins and peptides of spider Macrothele yani mainly inhabiting Yunnan province, China. Methods: Using a combination of RNA sequencing of the venom glands and venom proteomics based on Liquid Chromatography-Electrospray Ionization-Tandem Mass Spectrometry (LC-ESI-MS/MS), we provide the first overview of the peptides and proteins synthesized from Macrothele yani. Results: A total of 116 peptide sequences were analyzed, and 43 homologous proteins were matched, of which 38.10% were toxin proteins. High-throughput sequencing by the HiSeq-2000 (Illumina), followed by de novo assembly. As a result, 301,024 similar protein sequences were annotated in the available databases. A total of 68 toxins-related sequences were identified, comparative sequence analyses of these sequences indicated the presence of different types of enzymes and toxin- like genes, including Acetylcholinesterase, Hyaluronidase, cysteine-rich secretory proteins (CRISP), Astacin metalloprotease and other venom components. Conclusion: The venom of a spider is a very abundant resource in nature. They were analyzed to determine their function in pathophysiology. Molecular templates with potential application value in medical and biological fields were obtained by classifying and characterizing the presumed components of spider venom of Macrothele yani, which laid a foundation for further study of the venom in the future.

Phenolic compounds (PCs) could be applied to reduce reactive oxygen species (ROS) levels, and are used to prevent and treat diseases related to oxidative stress. QSAR study was applied to elucidate the relationship between the molecular descriptors and physicochemical properties of polyphenol analogues and their DPPH radical scavenging capability, to guide the design and discovery of highly-potent antioxidant substances more efficiently. PubMed database was used to collect 99 PCs with antioxidant activity, whereas, 105 negative PCs were found in ChEMBL database; their molecular descriptors were generated with Python's Rdkit package. While the molecular descriptors significantly related to the antioxidant activity of PCs were filtered by t-test. The prediction QSAR model was then established by discriminant analysis, and the obtained model was verified by the back-substitution and Leave-One-Out cross-validation methods along with heat map. It was revealed that the anti-DPPH radical activity of PCs was correlated with the drug-likeness and molecular fingerprints, physicochemical, topological, constitutional and electronic property. The established QSAR model could explicitly predict the antioxidant activity of polyphenols, thus were applicable to evaluate the potential of candidates as antioxidants.

Two new diketopiperazines (1, 2), one new polyprenol (3), together with 19 known compounds (4-22) were obtained from the EtOAc extract of Bionectria sp. Y1085, an endophytic fungus isolated from the plant Huperzia serrata. Their structures were elucidated by extensive NMR and MS analysis. Bionectin D (1) is a rare diketopiperazine with a single methylthio substitution at the α-carbon of cyclized amino acid residue. The antibacterial activity of compounds was assayed against Escherichia coli, Staphylococcus aureus, and Salmonella typhimurium ATCC 6539, and some metabolites (1, 2, 10, 11, and 14) exhibited evident antibacterial activity.

Magnaporthe grisea is the causal agent of rice blast disease, which is the most serious disease of cultivated rice. Aromatic polyketides are its typical metabolites and are involved in the infection process. In the search for novel lead compounds, chemical investigation of the fungus M. grisea M639 has led to the isolation of four new aromatic polyketides (salicylaldehyde skeleton bearing an unsaturated side chain), griseaketides A&ndash, D (1&ndash, 4), as well as 15 known compounds (5&ndash, 19). The structures of the new compounds were elucidated on the basis of extensive spectroscopic analyses, including HR-MS, 2D NMR. Compound 12 showed prominent activity that killed 94.5% of C. elegans at 400 ppm and 66.9% at 200 ppm over 24 h. This is the first report describing the nematicidal activity of this type aromatic polyketide.

Plants belonging to the genus Leonurus, also named motherwort, are traditionally used for anti-gynecological disorder in East Asia, and for sedative in Europe. Chemical investigation of the genus Leonurus not only enriched the natural products library, but also enlarged the pharmacological application of this traditional herb. In this review, we systematically summarized the structures of 259 compounds isolated from the genus Leonurus, featured with 147 labdane diterpenoids. The reported bioactivity studies up to 2017 are presented in the second part, with the main focus on the isolated compounds and also concerning the extracts. In addition to the traditional uterine contraction and sedative activity, recently the cardiovascular protection effect of leonurine has drawn most attention. Other than that, neuroprotection, anti-inflammation, anti-cancer, anti-platelet aggregation and many other activities have been assigned to various compounds from the genus Leonurus. Among 70 bioactivity references cited in this review, 57% of them were concentrated on two alkaloids (leonurine and stachydrine), whereas only 20% are about the 147 diterpenoids. Anti-inflammation is the major bioactivity discovered so far for the labdane diterpenoids from the genus Leonurus, whose further therapeutic potential still remains for exploration.

The determination of the absolute configuration of natural products still faces many challenges, especially the active pharmaceutical ingredient which is trace, oily and novel structures. Currently, NMR requires chiral reagents in determining the absolute configuration; ECD involves theoretical calculations and requires chromophores. In this study, the absolute configuration of asarinin had successfully identified by using synchrotron radiation with crystalline sponge method and combining MS with NMR. This method could identifying the crystal structure of trace amorphous substances, resolving the problem of absolute configuration of multi-chiral central compounds, and hopefully providing a new idea and approach for structural elucidation of natural products.

Besifloxacin is a fourth-generation broad-spectrum fluoroquinolone registered for the topical treatment of bacterial conjunctivitis. In this study, a rapid, sensitive and selective liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed for quantification of besifloxacin in rabbit plasma and ocular tissues using nateglinide as the internal standard (IS). The analyte and IS were separated on a Sepax GP-Phenyl column by isocratic elution with methanol-acetonitrile-5 mM ammonium formate-formic acid (29:55:16:0.1, v/v/v/v) as the mobile phase at a flow rate of 1.2 mL/min, and the total run time was 3.0 min. An electrospray ionization (ESI) source was applied and operated in the positive ion mode; multiple reaction monitoring (MRM) mode was used for quantification, and the monitored transitions were 394.2→377.1 for besifloxacin and m/z 318.3→166.1 for the IS. The calibration curve was linear over the range of 0.103-206 ng/mL for plasma and 2.06-2060 ng/mL for tears, aqueous humor, conjunctiva and cornea with correlation coefficient (r) greater than 0.99. The lower limit of quantification (LLOQ) for besifloxacin was 0.103 ng/mL for plasma and 2.06 ng/mL for other ocular tissues with good accuracy and precision. Intra- and inter-batch precision were both lower than 15% and accuracy ranged from 85% to 115% at all QC levels. The method was successfully applied to the pharmacokinetic study of besifloxacin in rabbit plasma and ocular tissues after single and multiple topical administrations.

A counterintuitive freezing-induced peptide ligation was discovered during the total synthesis of human interferon-e (hIFN-e) which blocks HIV infection through unique mechanisms. The successful synthesis of hIFN-e (187 amino acids) in this research laid the foundation for related anti-AIDS drug development. Moreover, alanine mutation based on sequence alignment to solve the maldistribution of the ligation site and freezing-induced dominant conformation that facilitates peptide ligation are expected to be helpful for the synthesis of macrobiomolecules.

In previous work, a series of bioactive natural products had been isolated from the plant endophytic Streptomyces sp. CS, which was isolated from Maytenus hookeri. To mine new active metabolites, we describe introducing an alien carbamoyltransferase (asm21) gene into the strain CS by conjugal transfer. As a result, three recombinatorial mutants named CS/asm21-1, CS/asm21-2 and CS/asm21-4 were successfully constructed. Three mutants and wild type CS were cultured on solid medium, and the extracts were detected and analyzed by liquid chromatography-mass spectrometry (LC-MS). The LC-MS profiles showed several unknown peaks that were present in the spectra of extracts of the CS/asm21-4 cultured on oatmeal solid medium. Then, three new naphthomycins O-Q (1-3), a new macrolide hookerolide (4) as well as nine known compounds were obtained from the solid cultured medium. Their structures were identified by spectra data. These new compounds showed moderate antimicrobial activities.

Objective To study the chemical constituents from the aerial parts of Hypericum beanii. Methods Various chromatographic techniques were used to separate the constituents and their structures were elucidated on the basis of extensive spectroscopic interpretation. Results Fifteen compounds were isolated from the aerial parts of H. beanii. Their structures were identified as hyperbeanol E (1), (E)-linalool-1-oic acid (2), (4S,5R)-5-(4′-methyl-3′-pentenyl)-4-hydroxy-5-methyl-dihydrofuran-2-one (3), benzoic acid (4), 4-(3-O-3′)-3′-methylbutenyl-6-phenyl-pyran-2-one (5), 4-hydroxy-4a,7-dimethoxy-4,4a-dihydrodibenzo-p-dioxin-2(3H)-one (6), isoimperatorin (7), 2,3-dimethoxyxanthone (8), 3,4-dihydroxy-2-methoxyxanthone (9), osajaxanthone (10), nigrolineaxanthone F (11), hypercohone G (12), betulinic acid (13), oleanolic acid 3β-caffeate (14), and isoastilbin (15). Conclusion Compound 1 is a new menthane monoterpene derivative which owns an extra lactone ring. Compounds 2–7 and 10–15 are isolated from genus Hypericum Linn. for the first time and the other compounds are first obtained from the plants in H. beanii.

A sensitive and selective liquid chromatography tandem mass spectrometric method was developed and validated for the simultaneous determination of five pyridine alkaloids contained in tripterygium glycosides tablets (triptolide, wilforine, wilforgine, wilfording and wilfortrine) in dog plasma. The analysis was carried out on a Sepax GP-Phenyl column using a mixture of methanol and 10mmol/L ammonium formate buffer solution containing 0.1% formic acid (75:25, v/v) as the mobile phase pumped at a flow-rate of 1.0mL/min. All MS data were obtained in the positive ESI mode with selective multiple reaction monitoring of ion transitions. The method was fully validated to be accurate and precise with a linear range of 0.2-1000ng/mL for triptolide and 0.05-1000ng/mL for the other four pyridine alkaloids. The intra-day and inter-day precisions (relative standard deviation, RSD, %) were within 10.6% and 14.0%, respectively, and the relative error (RE, %) were all less than 13.1%. The method was successfully applied to multi-components pharmacokinetic study of the five pyridine alkaloids in beagle dogs after a single oral administration of 3mg/kg and 30mg/kg tripterygium glycosides tablets, respectively, and a multiple oral administration of 30mg/kg for 6 consecutive days.

Objective To study the chemical constituents from the root barks of Morus alba . Methods Various chromatographic techniques were used to separate the constituents and their structures were elucidated on the basis of extensive spectroscopic interpretation. Results Six compounds were isolated from the root barks of M. alba . The structure of new compound, named as albafuran D ( 1 ), was established together with known compounds sanggenon H ( 2 ), kuwanon E ( 3 ), kuwanon U ( 4 ), kuwanon F ( 5 ), and benzokuwanon E ( 6 ). Conclusion Compound 1 is a new geranylated 2-arylbenzofuran.

Three new minor prenylated flavonoids, named macadenanthins A–C (1–3), together with three known ones (4–6), were isolated from the twigs of Macaranga adenantha. Their structures were elucidated on the basis of extensive spectroscopic analysis including NMR, UV and MS. The prenyl moieties in compounds 1–3 were further modified by cyclization and hydroxylation. The new compounds were tested for their cytotoxicity against four cancer cell lines (MCF-7, Hep G2, Hela and P388) and showed IC50 values in the range of 13.76–22.27 μM. Electronic supplementary material The online version of this article (doi:10.1007/s13659-015-0059-1) contains supplementary material, which is available to authorized users.

Two novel heterodimers, denticulatains A (1) and B (2), were isolated from the fronds of Macaranga denticulata. They possess an unprecedented stilbene–diterpene-type skeleton, which represents a unique class of prenylated stilbene. Their structures were elucidated by comprehensive analyses of extensive NMR and MS spectroscopic data. Compounds 1 and 2 exhibited inhibitory activity against acetylcholinesterase with the inhibition ratios of 22.1% and 27.5%, respectively, at a concentration of 50 μM.

One unique prenylated bibenzyl, kurzphenol A (1), two new prenylated flavonoids, kurzphenols B and C (2 and 3), as well as fourteen known compounds (4-17) were isolated from the twigs of Macaranga kurzii. Compound 1 was the first example of prenylated bibenzyl which possesses a benzofuran ring. All the known compounds were isolated from M. kurzii for the first time. Their structures were elucidated on the basis of extensive spectroscopic interpretation. Compounds 1-17 were tested for their cytotoxicity against A-549 and Hep G2 cancer cell lines and showed IC50 values in the range of 9.76-30.14 mu g/mL. (C) 2014 Elsevier B.V. All rights reserved.

Reversible phosphorylation of proteins is one of the most important post-translational modifications, while the detection of phosphopeptides is difficult due to their low abundance and the signal suppression of nonphosphorylated peptides. Therefore, selective enrichment of phosphopeptides from highly complicated mixtures is vital for MS-based phosphoproteome analysis. Despite various strategies have been developed, there is no single method that is capable of providing full coverage of the whole phosphoproteome. Metal oxide affinity chromatography (MOAC) enrichment preferably singly phosphopeptides, whereas immobilized metal affinity chromatography (IMAC) enrichment bias towards multiply phosphopeptides. In this study, first example of IMAC and MOAC hybrid material, Fe3O4@nSiO2@mSiO2/TiO2-Ti4+ nanoparticles were successfully synthesized for the enrichment of phosphopeptides with the aim to combining their advantages for enrich both mono- and multi-phosphorylated species. The TiO2 was firstly coated on the surface of mesoporous silica and then grafted with 3-(trihydroxysilyl)propyl methylphosphonate (THPMP) to chelate Ti4+ ions. This novel type of hybird material with high surface areas (179.3m2/g) exhibited good adsorption capacity (133mg/g) towards standard tryptic digest of β-casein and the method based on this material also showed good sensitivity (4pmol). The synthesized Fe3O4@nSiO2@mSiO2/TiO2-Ti4+ microspheres were further used to selectively enrich phosphopeptides from complex biosamples, seven mono-phosphopeptides and eight multi-phosphopeptides were successfully enriched from nonfat milk which is much better than single IMAC or MOAC strategy. Those results indicated that Fe3O4@nSiO2@mSiO2/TiO2-Ti4+ microspheres have potential applications in MS-based phosphoproteomics to enlarge phosphoproteomics coverage and this work was expected to open up a promising strategy which combined the advantages of various methods in one material for effective enrich phosphorylated peptides.

Phytochemical investigation of the aerial parts of Euphorbia sikkimensis led to the isolation of one new diterpenoids, named sikkimenoid E (1), together with thirteen other known compounds (2–14). Their structures were established by means of spectroscopic methods. Compound 2 was identified to be a trinortriterpenoid, and derived for the first time from a natural source. In this paper we reveal for the first time its comprehensive spectral data and NMR spectral assignment. Compound 4 showed antiangiogenic activity with an IC50 value of 5.66 µM in a zebrafish model, and compounds 5 and 6 exhibited cytotoxicity toward A549 cell line with IC50 values of 12.12 and 6.45 µM, respectively. Electronic Supplementary Material Supplementary material is available for this article at 10.1007/s13659-013-0006-y and is accessible for authorized users.

Four new jatropholane-type diterpenes (1-4), named sikkimenoids A-D, were isolated from the aerial parts of Euphorbia sikkimensis. The structural elucidations of 1-4 were accomplished by extensive NMR analyses, and their absolute configurations were established by ECD calculations. Compound 2 exhibited weak antiangiogenic activity with an IC(50) value of 43.0 μM when evaluated using a zebrafish model.

One rare diterpenoid which was an unusual phorbol derivative possessing a 5-ene-7-oxo functional group, wallichiioid A (1), and 17 known compounds (2-18) were isolated from the aerial parts of Euphorbia wallichii. The structures and relative configuration of these compounds were elucidated on the basis of extensive spectroscopic interpretation. All the known compounds were isolated from E. wallichii for the first time. Diterpenoids 1-5 were tested for their cytotoxicity against five cancer cell lines (A-549, MCF-7, Hep G2, HeLa, and P388) and showed IC(50) values in the range of 8.19-29.72 μg/mL. The antiangiogenic activities of diterpenoids 1-5 were also evaluated using a zebrafish model.

The heterodimers, denticulatains A (I) and B (II), possessing an unprecedented stilbene-diterpene-type skeleton are isolated from the fronds of Macaranga denticulata.

One rare flavonoid-diterpene heterodimer, denticulatain C (1), one modified geranyl-type side chain substituted flavonoid, denticulatain D (2) and one geranylated flavonoid, denticulatain E (3), as well as 11 known compounds (4-14) were isolated from the fronds of Macaranga denticulate. Their structures were elucidated on the basis of extensive spectroscopic interpretation. Compounds 4 and 8 inhibited the proliferation of A-549 cell line with IC50 values of 48.6 and 20.2 mu g/mL, respectively. Compounds 3, 6, and 8 exhibited significant antiangiogenic activity on a zebrafish model with IC50 values of 9.78, 034, and 2.55 mu g/mL, respectively. (C) 2015 Elsevier B.V. All rights reserved.

Three new prenylated flavonoids, macarindicins A-C (1-3), as well as seven known compounds (4-10) were isolated from the twigs of Macaranga indica. Their structures were elucidated on the basis of extensive spectroscopic interpretation. Compounds 2 and 3 enriched the diversity of prenyl moiety in genus Macaranga especially in the aspect of various lengths of prenyl chain. All the known compounds were isolated from M. indica for the first time and this plant was found to contain large number of ellagic acid. Compounds 1-10 were tested for their cytotoxicity against four cancer cell lines (MCF-7, Hep G2, Hela and P388) and showed IC50 values in the range of 2.61-20.35 mu g/mL. (C) 2015 Elsevier B.V. All rights reserved.

One rare diterpenoid which was an unusual phorbol derivative possessing a 5-ene-7-oxo functional group, wallichiioid A (1), and 17 known compounds (2–18) were isolated from the aerial parts of Euphorbia wallichii. The structures and relative configuration of these compounds were elucidated on the basis of extensive spectroscopic interpretation. All the known compounds were isolated from E. wallichii for the first time. Diterpenoids 1–5 were tested for their cytotoxicity against five cancer cell lines (A-549, MCF-7, Hep G2, HeLa, and P388) and showed IC50 values in the range of 8.19–29.72 μg/mL. The antiangiogenic activities of diterpenoids 1–5 were also evaluated using a zebrafish model.

Three new diterpenoids, stracheyioids A-C (1-3), as well as 36 known compounds (4-39) were isolated from the whole plants of Euphorbia stracheyi. Compound 1 was a rare 13-deoxy tigliane diterpenoid and compound 2 was an ingenol diterpenoid characterized by an unique 2Z,4Z-decadienoyl acidic moieties. All the known compounds were isolated from E. stracheyi for the first time. Their structures were elucidated on the basis of extensive spectroscopic interpretation. Compounds 1-39 were tested for their cytotoxicity against five cancer cell lines (A-549, MCF-7, Hep G2, Hela and P388) and showed IC50 values in the range 6.64-42.86 mu M. The antiangiogenic activities of the isolated compounds were also evaluated using a zebrafish model. (C) 2014 Elsevier B.V. All rights reserved.

Sixteen compounds were isolated from the aerial parts of Euphorbia sikkimensis by means of various chromatographic techniques such as silica gel, Sephades LH-20 and RP-18, and their structures were elucidated as naringenin (1), kaempferol (2), quercetin (3), kaempferol-3-O-alpha-L-arabinopyranoside (4), quercetin-3-O-alpha-L-arabinopyranoside (5), quercetin-3-O-(2"-galloyl)-alpha-L-arabinopyranoside (6), 5alpha, 8alpha-epidioxy-(22E, 24R)-ergosta-6,22-dien-3beta-ol (7), stigmast-5-ene-7-one-3beta-ol (8), 3beta-hydroxy4a, 14alpha-dimethyl-5alpha-ergosta-8, 24(28)-dien-7-one(9), beta-sitosterol (10) , 10-cucurbitadienol( 1) , scopoletin(12) , ethyl gallate(13), p-hydroxybenzaldehyde (14), 3 betahydroxybenzeneethanol( 15) ,and 2,4-dihydroxy-6-methoxy-acetophenone (16) on the basis of spectroscopic data analysis. All the compounds are isolated from this plant for the first time, and compounds 1, 4-8, 15 are obtained from Euphorbia species for the first time.

To study the chemical constituents of Gastrodia elata.The compounds were isolated by silica gel column chromatography and recrystallization and their structures were elucidated by spectral analysis.The structures of 14 compounds were identified as: p-hydroxybenzyl alcohol (1), p-hydroxybenzaldehyde (2), 3, 4-dihydroxybenzaldehyde (3), 4, 4'-dihydroxy, dibenzyl ether (4), 4-hydroxymethyl benzyl-4'-hydroxy-3'-(4"-hydroxy benzl) benzyl ether (5), 4-ethoxybenzyl alcohol (6), anisic alcohol (7), bis(3, 4-dihydroxyphenyl) methane (8), 4, 4'-dihydroxydiphenyl methane (9), 2, 4-bis(4'-hydroxy-benzyl)-phenol (10), 4-( methoxymenthyl) benzene-1, 2-diol (11), p-methylphenyl-1 -O-beta-D-glucopyranoside (12), N6-(4'-hydroxybenzl) -adenosine (13) and beta-sitosterol (14).Compounds 6 - 8 and 11 are isolated from this plant for the first time.