查看更多>>摘要：Bioactive compounds with angiotensin-I converting enzyme attenuation potential are deemed as therapeutic agents for hypertension owing to their capacity to suppress the conversion of angiotensin-I into the vasoconstrictor angiotensin-II. In an aim to develop natural angiotensin-I converting enzyme (ACE-I) inhibitors from marine algae, three 6, 6-spiroketals, spirornatas A-C were isolated from the organic extract of the spiny brown marine macroalga Turbinaria ornata (Turner) (family Sargassaceae). Spirornata A exhibited comparatively greater ACE-I attenuation potential (IC50 4.5 mu M) than those displayed by other studied spiroketals (IC50 4.7-4.9 mu M), and its activity was comparable to the ACE inhibitory agent captopril (IC50 4.3 mu M). Greater antioxidant properties of spirornata A against oxidants (IC50 1.1-1.3 mM) also substantiated its potential attenuation property against ACE-I. Structure-activity correlation studies showed that electronic properties (topological polar surface area, 71) and balanced hydrophilic-lipophilic parameters (partition coefficient of logarithmic octanolwater similar to 3.2) of spirornata A appeared to play pivotal roles in the inhibition of the targeted enzyme. Predicted drug-likeness and other physicochemical parameters appeared to attribute to the acceptable oral bioavailability of spiroketal derivatives. Additionally, the least binding energy of spirornata A with ACE-I (-10.5 kcal/mol) coupled with the maximum number of hydrogen-bonding interactions with allosteric sites of the zinc-dependent dicarboxypeptidyl peptidase could recognize its potential therapeutic application against hypertensive diseases.
查看更多>>摘要：Eight undescribed triterpenoids (pterohoonoids A H) including four oleananes, one nor-oleanane and three norursanes, along with seven known analogues, were isolated from the whole plants of Pterocephalus hookeri (Dipsacaceae). The structures with relative stereochemistries of these molecules were elucidated mainly by spectroscopic analyses, and the absolute configurations of the undescribed ones were assigned by a variety of methods, including time-dependent density functional theory (TD-DFT) based electronic circular dichroism (ECD) calculation, Rh-2(OCOCF3)4-induced ECD experiment and chemical transformation. The inhibitory effects toward the diabetes target alpha-glucosidase of all the isolates were assessed, and four of them exhibited pronounced activity with IC50 values ranging from 6.8 to 55.8 mu M. In addition, four compounds also showed inhibition against the nitric oxide (NO) production induced by lipopolysaccharide (LPS) in RAW264.7 macrophage cells (IC50 = 12.4-63.7 mu M). Further assays demonstrated that the most active compound pterohoonoid A inhibited the release of two key pro-inflammatory cytokines TNF-alpha and IL-6 in a dose-dependent manner.
查看更多>>摘要：Lemongrass essential oil has antifungal and anti-cancerous properties. Heat-shock protein (HSP90), an ATPdependent molecular chaperone found in eukaryotes, is involved in protein folding, stability, and disease, making it a promising research topic. Both in silico and in vitro approaches were used to provide a clear insight into the HSP90-ATPase 3D structures, activity, and their interaction with the essential oil constituents among various species such as fungi (S. cerevisiae), parasites (P. falciparum), and humans. For in silico studies, sequence alignment, docking (AutoDock), and absorption, distribution, metabolism, and excretion (ADME) properties were evaluated to obtain hit compounds specifically against each HSP90-ATPase. The hit compounds obtained were evaluated for their efficacy in the in vitro studies of S. cerevisiae. In vitro studies were carried out targeting HSP90-ATPases via lemongrass essential oil components individually and in combination as a function of concentration and various salt concentrations. Results suggest that sequence alignment exists of over 75% among these three species. The best docking score was possessed by Geraniol and its constituent (geldanamycin >= -4.93 kcal/mol) (a known antifungal and antitumor against HSP90) in all the above species. Lemongrass oil and the combination of Geraniol and Citral at concentrations of 80 mu g/mL showed the maximum inhibition of ATPase and HSP90-ATPase activity compared to their individual treatment. Therefore, both in silico and in vitro studies provide clear evidence of specific inhibitory action of lemongrass oil, Geraniol, and Citral against the ATPase and HSP90-ATPase activities and might show potential as antifungal and antitumor drugs.
查看更多>>摘要：Bletilla striata is a precious traditional Chinese medical herb with a wide range of applications in pharmacological and cosmetic fields. Because of the shortage of resources, Bletilla ochracea and Bletilla formosanare are also used as the substitutes. To distinguish the differences and homologies, the typical morphologic and microscopic characteristics of them were compared, and a UPLC fingerprint analysis coupled with chemometric methods were developed for characterization and quality evaluation of Bletillae Rhizoma. Gastrodin, protocatechuic acid, gymnoside V, blestrianol A, coelonin, gymnosides IX and batatasin II were identified as the potential chemical markers for comprehensive quality evaluation by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). The anti-melanogenic activities of the three species were also compared for the first time in vivo using the zebrafish model, the results suggested that B. striata and its two substitutes had obvious anti-melanogenic activities, and they were not-toxic at depigmenting doses. Molecular docking studies revealed batatasin III, blestrianol A, coelonin, and gastrodin were possible multitarget compounds associated with melanogenesis suppression, which are important for their potential future medical application.
查看更多>>摘要：Development of the kiwifruit industry has been severely hindered by the canker disease, which is caused by the bacterium Pseudomonas syringae pv. Actinidiae (Psa). However, endophytic fungi associated with healthy kiwi plants may protect host plants through the production of metabolites with potent anti-Psa activity. In the current study, four undescribed isobenzofuranones, namely sporulactones A-D, two undescribed isocoumarins, namely sporulactones E and F, together with eight known analogs were isolated from the kiwi endophytic fungus Paraphaeosphaeria sporulosa. The structures with absolute configurations were established by extensive spectroscopic methods, quantum chemistry calculations, and X-ray diffraction experiments. In addition, five of the compounds exhibited anti-Psa activity, with minimum inhibitory concentration (MIC) values ranging from 25 to 100 mu g/mL. These findings suggest that the small polyketide metabolites produced by P. sporulosa play an important role in the antibacterial properties of the endophyte.
查看更多>>摘要：About 95% of fatal mushroom poisonings worldwide are caused by amatoxins and phallotoxins mostly produced by species of Amanita, Galerina, and Lepiota. The genus Lepiota is supposed to include a high number of species producing amatoxins. In this study, we investigated 16 species of Lepiota based on 48 recently collected specimens for the presence of amatoxins by liquid chromatography coupled to a diode-array detector and mass spectrometry (UHPLC-QTOF-MS/MS). By comparing the retention times, UV absorptions, and diagnostic MS fragment ions with data obtained from the benchmark species Amanita phalloides, we detected alpha-amanitin and gamma-amanitin in Lepiota subincarnata, alpha-amanitin and amaninamide in Lepiota brunneoincarnata, and beta-amanitin and alpha-amanitin in Lepiota elaiophylla. Phallotoxins have not been detected any of these species. Two possibly undescribed amatoxin derivatives were found in Lepiota boudieri and L. elaiophylla, as well as one further nonamatoxin compound in one specimen of L. cf. boudieri. These compounds might be used to differentiate L. elaiophylla from L. xanthophylla and species within the L. boudieri species complex. No amatoxins were detected in L. aspera, L. castanea, L. clypeolaria, L. cristata, L. erminea, L. felina, L. fuscovinacea, L. lilacea, L. magnispora, L. oreadiformis, L. pseudolilacea, L. sp. (SeSa 5), and L. subalba. By combining the occurrence data of amatoxins with a phylogenetic analysis, a monophyletic group of amatoxin containing species of Lepiota is evident. These chemotaxonomic results highlight the relevance of systematic relationships for the occurrence of amatoxins and expand our knowledge about the toxicity of species of Lepiota.
Mohamed, Nesma M.Ahmed, Mai A. M.Khan, Shabana, IFronczek, Frank R....
10页
查看更多>>摘要：In our ongoing effort to investigate active specialised metabolites from genus Glandularia, phytochemical studies on the ethanolic extract of Glandularia x hybrida (Groenl. & Rumpler) G.L. Nesom & Pruski leaves resulted in the isolation of three undescribed compounds, a dibenzylbutyrolactolic lignan and two echinocystic acid based triterpenoid saponins, in addition to two known compounds. Interestingly, this study reports isolation of chemosystematically valuable specialised metabolites for the first time from the genus under investigation. Additionally, the isolated metabolites were evaluated for their iNOS inhibition and cytotoxic activities using a combination of in silico and in vitro studies. The pharmacokinetics properties (ADMET) of some of the isolated compounds were determined using pkCSM-pharmacokinetics server. Molecular docking analysis showed that saponin compound possesses higher negative score (-9.59 kcal/mol) than the lignan compound (-6.56 kcal/ mol). The isolated compounds also showed iNOS inhibition activity with IC50 values ranging between 6.6 and 49.7 mu M and significant cytotoxic activity against a series of cell lines including SK-MEL, KB, BT-549, SK-OV-3, LLC-PK1 and VERO cells. Hence, this study reveals that specialised metabolites from G. hybrida plant are of significant anti-inflammatory and cytotoxicity potentials.
查看更多>>摘要：Phytochemical investigation of the ethanol extract from wild Momordica charantia vines has resulted in isolation of seven cucurbitane-type triterpenoids, including six undescribed compounds, kuguaovins H.M, and the known compound, momordicoside K. The structures of the isolated compounds were elucidated on the basis of spectroscopic analyses, including 1D and 2D NMR, and MS experiments. The chemical structure of momordicoside K was determined for the first time by X-ray crystallographic analysis and its absolute configuration assigned. The cytotoxicity against four human tumor cell lines and anti-inflammatory activities on LPS-stimulated RAW264.7 macrophages were evaluated. Of the isolates, kaguaovin L exhibited potential cytotoxicity against MCF-7, HEp-2, Hep-G2, and WiDr cancer cell lines and showed moderate anti-NO production activity. In addition, kuguaovins H and J also showed the stimulatory effect of GLP-1 secretion on the murine intestinal secretin tumor cell line (STC-1).
Doffek, BenjaminHuang, YvonneHuang, Yen-HuaChan, Lai Yue...
10页
查看更多>>摘要：Cyclotides are a class of ribosomally-synthesized plant peptides that function in plants as a defense against insects and fungal pathogens. Their unique structure comprises a cyclized peptide backbone threaded by three disulfide bonds, that imparts structural stability, a desirable quality for peptide-based therapeutics or insecticides. Producing these peptides synthetically is challenging due to the amount of chemical waste produced and inefficiency of folding certain cyclotides. Thus, it is desirable to develop a means to access cyclotide biosynthesis in their native hosts, cultured in defined conditions, at both laboratory and commercial scale. Here we developed suspension cell cultures from two species previously unexplored for cyclotide production in suspension cells, Clitoria ternatea L., Hybanthus enneaspermus F. Muell., as well as with Oldenlandia affinis (Roem. & Schult.) DC., a species reported previously to accumulate cyclotides in cell suspensions. We assessed the growth rate, cyclotide production and gene expression for the various species. We found that while many cyclotides had reduced expression in Oldenlandia affinis suspension cells when compared to plant organs, those in Clitoria ternatea and Hybanthus enneaspermus maintained or increased expression levels. The cyclotides that continued to be expressed in suspension cultures shared similar sequence and biophysical properties as a group, regardless of phylogenetic origin of the host. Of particular interest was the discovery of inducibility by NaCl of cyclotide expression in O. affinis, cycloviolacin O2 expression in O. affinis, and the scale up of cycloviolacin O2 production in H. enneaspermus. Together the results presented here highlight the utility of plant cell suspensions as modalities to produce macrocyclic peptides.
Campos, O. Rene ArredondoBannon, Catherine C.de la Mata, A. PaulinaCase, Rebecca J....
8页
查看更多>>摘要：Dunaliella tertiolecta is a marine microalgae that has been studied extensively as a potential carbon-neutral biofuel source (Tang et al., 2011). Microalgae oil contains high quantities of energy-rich fatty acids and lipids, but is not yet commercially viable as an alternative fuel. Carefully optimised growth conditions, and more recently, algal-bacterial co-cultures have been explored as a way of improving the yield of D. tertiolecta micro algae oils. The relationship between the host microalgae and bacterial co-cultures is currently poorly understood. Here, a complete workflow is proposed to analyse the global metabolomic profile of co-cultured D. tertiolectra and Phaeobacter italicus R11, which will enable researchers to explore the chemical nature of this relationship in more detail. To the best of the authors' knowledge this study is one of the first of its kind, in which a pipeline for an entirely untargeted analysis of the algal metabolome is proposed using a practical sample preparation, introduction, and data analysis routine.
NSTL
Elsevier