Synthesis and biological activity of the probable biosynthetic precursors of 241-norbrassinolide

A series of 24¹-norbrassinolide biosynthetic precursors containing 3??-OH, 3-keto, ??²- or 2??,3??-epoxy functional groups less polar than 2??,3??-diol group in A-ring, and (22R,23R)-diol group in the side chain, was synthesized. Their biological activity as the proliferation regulators in MCF-7 human breast cancer and LNCaP human prostate adenocarcinoma cells was studied. It was shown that the majority of the derivatives obtained effectively suppress cell proliferation. The dependence of proliferation on the concentration of the studied compounds was found in LNCaP human prostate adenocarcinoma cells (IC₅₀ = 13?C28 ??M at 72 h of incubation in a medium containing 10% FBS, and suppression of DNA biosynthesis). Some compounds stimulated apoptosis (23?C33%), blocked the cell cycle in S- and G2/M-phases, and induced a partial detachment of cells during a prolonged incubation.     

Investigation of chemical constituents from Spiraea prunifolia var. simpliciflora and their biological activities

Quantum mechanics (QM)-based calculations for elucidating full structures of natural compounds are growing in importance and reliability. Two new phenolic glycosides (1 and 2) and 11 known compounds were isolated from the twigs of Spiraea prunifolia var. simpliciflora. The chemical structures of the new compounds (1 and 2) were initially established through different NMR techniques (¹H and ¹³C NMR, COSY, HSQC, and HMBC), HRMS data analysis, and chemical hydrolysis. These structure assignments were further verified by QM-based NMR chemical shift calculations. All of the purified compounds (1–13) were evaluated for their cytotoxicity against four human cancer cell lines (A549, SK-OV-3, SK-MEL-2, and BT549). Those phytochemicals were also evaluated for both anti-inflammatory activity through the measurement of nitric oxide (NO) production levels in lipopolysaccharide (LPS)-stimulated murine microglia BV-2 cell lines and neuroprotective effects via induction of nerve growth factor (NGF) in C6 glioma cells.     

Bioactive triterpenoids from twigs of Betula schmidtii

Investigation of the MeOH extract of Betula schmidtii twigs resulted in the isolation and identification of three new triterpenoids (1–3), along with ten known ones (4–13). The structures of new compounds (1–3) were elucidated by spectroscopic methods, including 1D, 2D NMR (¹H and ¹³C NMR, COSY, HSQC, HMBC, and NOESY), HR-MS, and chemical methods. All the isolated compounds were evaluated for their cytotoxicity against A549, SK-OV-3, SK-MEL-2, and HCT-15 cell lines. Compound 11 exhibited potent cytotoxic activities against four cell lines, and compounds 5 and 13 significantly induced nerve growth factor secretion in a C6 rat glioma cell line. Their anti-inflammatory effects were also assessed by measuring nitric oxide production in lipopolysaccharide–activated BV-2 cells. Compounds 7 and 12 displayed potent inhibition of nitric oxide production, without significant cell toxicity.     

Anticancer activity in vitro of a fucoidan from the brown alga Fucus evanescens and its low-molecular fragments, structurally characterized by tandem mass-spectrometry

Fucoidan was isolated and purified from the brown algae Fucus evanescens and subjected to autohydrolysis to obtain low-molecular-weight fragments. MALDI-TOFMS analysis has shown that monosulfated fucose and more heavily sulfated (up to 5) fucooligosaccharides with polymerization degree (DP) 2, 4 and 6, including galactose-containing sulfated oligosaccharides were the products of autohydrolysis. The structural features of these fragments were elucidated by negative-ion potential lift tandem MALDI-TOF mass-spectrometry using arabinoosazone as a matrix, which allowed reducing the in-source fragmentation. Native fucoidan has been shown to exert anticancer activities in both human malignant melanoma cell lines SK-MEL-28 and SK-MEL-5. Low-molecular-weight fragments exhibited almost no action to cell proliferation in both cell lines and colony formation on SK-MEL-5 cells, but its inhibition activity to the colony formation of SK-MEL-28 cell lines was as high as was demonstrated by native fucoidan (70%). Probably, the inhibiting activity for SK-MEL-28 depended on the presence of sulfates and (1 → 4)-linked α-l-Fucp residues in the main chain of fucoidan/oligosaccharides.     

Anticancer profile of newly synthesized BRAF inhibitors possess 5-(pyrimidin-4-yl)imidazo[2,1-b]thiazole scaffold

In this work, a new series of imidazo[2,1-b]thiazole was designed and synthesized. The new compounds are having 3-fluorophenyl at position 6 of imidazo[2,1-b]thiazole and pyrimidine ring at position 5. The pyrimidine ring containing either amide or sulphonamide moiety attached to a linker (ethyl or propyl) at position 2 of the pyrimidine ring. The final compounds were selected by NCI for in vitro cytotoxicity screening. Most derivatives showed cytotoxic activity against colon cancer and melanoma cell lines. In addition, IC₅₀s of the target compounds were determined over A375 and SK-MEL-28 cell lines using sorafenib as positive control. Compounds12b, 12c, 12e, 12f, 15a, 15d, 15f, 14g and 15h exhibited superior activity when compared to sorafenib. The most potent compounds were tested against wild type BRAF, v600e BRAF, and CRAF. Compound 15h exhibited a potential inhibitory effect against^V600EBRAF (IC₅₀?=?9.3?nM).     

Two new phenolic compounds from the white flower of Impatiens balsamina

During the course of our continuing search for biologically active compounds from Korean medicinal sources, we investigated the white flower of Impatiens balsamina. From the MeOH extract, two new phenolic compounds (1–2) containing a nitrile group and eleven known phenolic compounds (3–13) were isolated. The chemical structures of new compounds (1–2) were determined through NMR, HRMS, and CD data. We tested the isolated compounds (1–13) for their cytotoxic activities by determining their inhibitory effects on human tumor cell lines (A549, SK-OV-3, SK-MEL-2, and HCT15) in vitro using the sulforhodamine B (SRB) assay. We also investigated their neuroprotective activity by determining their effects on nerve growth factor (NGF) secretion in C6 cells, and anti-neuroinflammatory activity by measuring nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated BV-2 cells.     

Discrimination of the rare medicinal plant Dendrobium officinale based on naringenin, bibenzyl, and polysaccharides

The aim of this study was to establish a method for discriminating Dendrobium officinale from four of its close relatives Dendrobium chrysanthum, Dendrobium crystallinum, Dendrobium aphyllum and Dendrobium devonianum based on chemical composition analysis. We analyzed 62 samples of 24 Dendrobium species. High performance liquid chromatography analysis confirmed that the four low molecular weight compounds 4??,5,7-trihydroxyflavanone (naringenin), 3,4-dihydroxy-4??,5-dime-thoxybibenzyl (DDB-2), 3??,4-dihydroxy-3,5??-dimethoxybibenzyl (gigantol), and 4,4??-dihydroxy-3,3??,5-trimethoxybibenzy (moscatilin), were common in the genus. The phenol-sulfuric acid method was used to quantify polysaccharides, and the monosaccharide composition of the polysaccharides was determined by gas chromatography. Stepwise discriminant analysis was used to differentiate among the five closely related species based on the chemical composition analysis. This proved to be a simple and accurate approach for discriminating among these species. The results also showed that the polysaccharide content, the amounts of the four low molecular weight compounds, and the mannose to glucose ratio, were important factors for species discriminant. Therefore, we propose that a chemical analysis based on quantification of naringenin, bibenzyl, and polysaccharides is effective for identifying D. officinale.     

Novel metabolites from the roots of Cadaba natalensis

From an extract of the roots of Cadaba natalensis Sond. the novel macrocyclic dibenzo-diazacyclododecanedione 1 was isolated together with (S)-2-ethyl-2-methyloxazolidin-5-one (2a). In addition, the five known compounds were obtained. Of these, (R)-5-ethyl-5-methyloxazolidin-2-one (3) is reported as a natural product for the first time. The structures of the isolated compounds were elucidated by analysis of the spectral data, 1D NMR (¹H, ¹³C, and DEPT), 2D NMR (COSY, HMQC, HMBC, and NOESY), and HRESIMS, as well as by the comparison with previously reported data.     

Antagonizing canonical Wnt signaling pathway by recombinant human sFRP4 purified from E. coli and its implications in cancer therapy

During the last two decades, new insights into proteasome function and its role in several human diseases made it a potential therapeutic target. In this context, Amblyomin-X is a Kunitz-type FXa inhibitor similar to endogenous tissue factor pathway inhibitor (TFPI) and is a novel proteasome inhibitor. Herein, we have demonstrated Amblyomin-X cytotoxicity to different tumor cells lines such as pancreatic (Panc1, AsPC1BxPC3) and melanoma (SK-MEL-5 and SK-MEL-28). Of note, Amblyomin-X was not cytotoxic to normal human fibroblast cells. In addition, Amblyomin-X promoted accumulation of ER stress markers (GRP78 and GADD153) in sensitive (SK-MEL-28) and bortezomib-resistant (Mia-PaCa-2) tumor cells. The intracellular calcium concentration [Ca²⁺] _i was slightly modulated in human tumor cells (SK-MEL-28 and Mia-PaCa-2) after 24 h of Amblyomin-X treatment. Furthermore, Amblyomin-X induced mitochondrial dysfunction, cytochrome-c release, PARP cleavage, and activation of caspase cascade in both human tumor (SK-MEL-28 and Mia-PaCa-2) cells. These investigations might help in further understanding of the antitumor properties of Amblyomin-X.     

Bioactivity-guided isolation of cytotoxic triterpenoids from the trunk of Berberis koreana

A bioassay-guided fractionation and chemical investigation of the trunk of Berberis koreana resulted in the isolation and characterization of two new triterpenoids, 23-trans-p-coumaroyloxy-2α,3α-dihydroxyolean-12-en-28-oic acid (1), and 23-cis-p-coumaroyloxy-2α,3α-dihydroxyolean-12-en-28-oic acid (2), along with seven known triterpenoids (3–9). The structures of the new compounds were determined on the basis of spectroscopic analyses including 2D NMR. The cytotoxic activities of the triterpenes (1–9) were evaluated by determining their inhibitory effects on human tumor cell lines (A549, SK-OV-3, SK-MEL-2, and HCT-15) using the SRB assay. Compounds 5 and 6 showed potent cytotoxicity against A549, SK-OV-3, SK-MEL-2, and HCT-15 cell lines (IC₅₀ (5): 4.37, 7.04, 9.72, and 5.83 μM, and IC₅₀ (6): 5.57, 7.84, 13.29, and 5.61 μM, respectively).     

Sulphides and furanones from steam volatile oils of Allium fistulosum and Allium chinense

The constituents of the steam volatile oils from two kinds of Allium fistulosum, A. fistulosum var. caespitosum and A. chinense, have been investigated by GC and spectral techniques (IR, UV, GC/MS, ¹H NMR and ¹³C NMR). The compounds identified from the neutral fraction of each volatile oil included sulphides, thiolanes, alcohols, aldehydes, ketones, furanones and others. Among the sulphur compounds, dipropyl disulphide comprised ca 28% of A. fistulosum oil, ca 23% of A. fistulosum var. caespitosum oil and ca 30% of A. chinense oil. A. fistulosum oil was characterized by a large quantity of tridecan-2-one (ca 52%) and 2,3-dihydro-2-octyl-5-methylfuran-3-one (ca 16%). Also, a large amount of 2,3-dihydro-2-hexyl-5-methylfuran-3-one (ca 20%) was isolated from A. chinense oil.     

Isolation of Fucoxanthin and Highly Unsaturated Monogalactosyldiacylglycerol from Brown Alga Fucus evanescens C Agardh and In Vitro Investigation of Their Antitumor Activity

Fucoxanthin (FX) and highly unsaturated monogalactosyldiacylglycerol (MGDG) were isolated from the ethanol extract of brown alga Fucus evanescens. Their structures were identified by nuclear magnetic resonance, complemented by electrospray ionization mass spectrometry (ESIMS). MGDG was identified as 1-O-(5Z,8Z,11Z,14Z,17Z-eicosapentanoyl)-2-O-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-3-O-β-d-galactopiranosyl-sn-glycerol. Antitumor activity of these compounds was tested on human melanoma (SK-MEL-28) cells. MGDG and FX inhibited the growth of human melanoma cells in a dose-dependent manner. IC₅₀ values for growth inhibition were 104 and 114 μM, correspondently.     

Synthesis and anticancer activity of new thiazolo[3,2-a]pyrimidines: DNA binding and molecular modeling study

A novel series of nitrogenous heterocycles starting from chalcones including thiazolo[3,2-a]pyrimidines (20–67), were synthesized. Structure elucidation of the synthesized compounds was attained by the use of ¹H NMR, ¹³CC NMR, and Mass spectrometry. The obtained compounds were evaluated for their in vitro anticancer activity at the National Cancer Institute (NCI) 60 cell lines panel assay. Three cell lines, non-small cell lung cancer Hop-92, ovarian cancer IGROV1, and melanoma SK-MEL-2, exhibited some sensitivity against most of the tested compounds. Six compounds have passed the 5-log dose level NCI assay. Compounds 34 and 24 proved to be the most active derivatives with GI₅₀, TGI, LC₅₀ of 5.89, 20.0, 66.1% and 5.0, 19.5, 52.5% respectively. Compounds 36, 39, 63 showed lesser activity with GI₅₀, TGI, LC₅₀ 3.2, 11.8, 38.9%, 3.4, 16.6, 60.3%, 3.5, 17.8, 66.1% respectively. DNA binding assay of synthesized compound were performed. Molecular docking showed that compounds 34, 42, and 60 could effectively fit into the minor groove and selectively bind with AT base pairs. The results could confer the anticancer activity of compounds 24, 34, 36, and 39 in vitro to their abilities to bind at DNA minor groove.     

Two new spirostanol saponins from the the roots and rhizomes of Tupistra chinensis

Two new spirostanol saponins (1) and (2), together with three known saponins (3–5), were isolated from the roots and rhizomes of Tupistra chinensis, and their structures were determined as (20S, 22R)-spirost-25(27)-en-1β, 3β, 4β, 5β-tetraol-5-O-β-d-glucopyranoside (1) and (20S, 22R)-spirost-25(27)-en-1β, 3β, 5β-triol-5-O-β-d-glucopyranoside (2), (20S, 22R)-spirost-25(27)-en-1β, 2β, 3β, 4β, 5β-pentaol-5-O-β-d-glucopyranoside (3), Δ²⁵⁽²⁷⁾-pentrogenin (4) and ranmogenin A (5) on the basis of physicochemical properties and spectral analysis. The isolated compounds were evaluated for their cytotoxic activities against A549 and H1299 tumor cell lines in vitro. Among them, compound 2 showed cytotoxicities against A549 cells (IC₅₀ 52.66 ± 3.12 μmol L⁻¹) and H1299 cells (IC₅₀ 57.29 ± 2.51 μmol L⁻¹), respectively.     

Three new compounds isolated from the bulbs of Fritillaria pallidiflora Schrenk and their anti-inflammatory activity

Three new compounds, 17β-cevanin-6-oxo-5α,20β-diol yibeinine (1), 2-(tetrahydro-5-(2-hydroxyphenyl)-2H-pyran-3-yl) phenol (2), 1,3-O-diferuloyl-2-methoxypropane diol (3), as well as four known compounds (4–7), have been isolated from the ethanol extract of dried bulbs of Fritillaria pallidiflora Schrenk. All structures were determined based on their spectroscopic data (1D and 2D NMR (including ¹H NMR, ¹³C NMR, ¹H-¹H COSY, HMBC, HSQC, HSQC-TOCSY, and NOESY experiments), and MS). Biological evaluation showed that compounds 1–4 inhibited the production of nitric oxide (NO) in LPS-stimulated RAW 264.7 cells with IC₅₀ values of 18.0, 38.7, 29.5, and 47.1 μM, respectively. These results indicated that compound 1 has potential anti-inflammatory activity.     

Benzylisoquinoline alkaloids from the tubers of Corydalis ternata and their cytotoxicity

Chemical investigation of the tubers of Corydalis ternata resulted in the isolation and characterization of four new benzylisoquinoline alkaloids, epi-coryximine (1) and coryternatines A–C (2–4), along with 10 known alkaloids (5–14). Their structures were established on the basis of extensive spectroscopic data analyses and comparison with spectroscopic data reported. In addition, the cytotoxicities of the alkaloids (1–14) were evaluated by determining their inhibitory effects on several human tumor cell lines (A549, SK-OV-3, SK-MEL-2, and HCT-15) using the SRB assay. Compound 8 showed significant cytotoxicity against A549, SK-OV-3, SK-MEL-2, and HCT-15 cell lines (IC₅₀ = 8.34, 5.14, 7.87, and 2.86 μM, respectively). The four new compounds (1–4) exhibited selective cytotoxicity against the HCT-15 cell line.     

Triterpenes and lignans from the leaves of Styrax tonkinensis

Two triterpenes (1 and 2) and eight lignans (3–10) were isolated from the ethyl acetate-soluble fraction of the leaves of Styrax tonkinensis (Pierre) Craib ex Hartw (Styracaceae). Their structures were established as ursolic acid (1), pomolic acid (2), 3,3′-bis(3,4-dihydro-6-methoxy-2H-1-benzopyran) (3), rac-(8α,8′β)-4,4′-dihydroxy-3,3′-dimethoxylignan-9,9′-diyldiacetate (4), (-)-secoisolariciresinol (5), (+)-pinoresinol (6), 4,4′-dihydroxy-3,3′-dimethoxy-9-ethoxy-9,9′-epoxylignan (7), (2S,3R, 4R)-4-[1-ethoxy-1-(4-hydroxy-3-methoxy)phenyl]methyl-2-(4-hydroxy-3-methoxy)phenyl-3-hydroxymethyl-tetrahydrofuran (8), (-)-neo-olivil-(9-O-9″)-seco-isolariciresinol (9) and isolariciresinol (10) based on MS, ¹H-and ¹³C-NMR spectral data. All these compounds (1–10) were firstly isolated from this plant, and compounds 2–5 and 7–9 were reported from the Styrax genus for the first time. Furthermore, the chemotaxonomic significance of the isolated compounds was discussed.     

Hexosediphosphatase from spinach chloroplasts: Purification,crystallization and some properties

Hexosediphosphatase (d-fructose-1,6-bisphosphate 1-phosphohydrolase, EC 3.1.3.11) has been isolated, purified, and crystallized, from previously isolated spinach chloroplasts. The effects of various anions, cations, and sulfhydryl compounds were tested, and activation by Mg²⁺, glycine, HCO₃^?, and sulfhydryl compounds is described. The purified enzyme is very specific for fructose 1,6-diphosphate and does not attack sedoheptulose-1,7-bisphosphate. The s₂₀ value of the enzyme was 7.7, from which the molecular weight of the enzyme was estimated as 140 000.     

Xanthone,benzophenone and bianthrone derivatives from the hypersaline lake-derived fungus Aspergillus wentii

Five new metabolites, including the xanthone derivative wentixanthone A (1), the benzophenone wentiphenone A (2), the diastereomeric mixtures of the bianthrones wentibianthrone A (3a, b) and wentibianthrone B (4a, b), as well as (10R,10′S)-wentibianthrone C (5a) and (10R,10′R)-wentibianthrone C (5b) were obtained from the fungus Aspergillus wentii, isolated from soil of the hypersaline lake El Hamra in Wadi El-Natrun, Egypt. The structures of the isolated compounds were established by one and two-dimensional NMR and MS spectroscopic analysis. The relative configuration of bianthrones (3–5) was elucidated by comparison of experimental and computed ¹H NMR chemical shifts. Results of biological assays are reported.     

Steroid compounds from the Far East starfish <Emphasis Type="Italic">Pteraster obscurus</Emphasis> and the ophiura <Emphasis Type="Italic">Asteronyx loveni</Emphasis>

Seven sulfated polyhydroxysteroids were isolated from the Far East starfish Pteraster obscurus and the ophiura (snake star) Asteronyx loveni (collected in the Sea of Okhotsk) and characterized: disodium and sodium salts of (20R)-24-methyl-2β-hydroxycholesta-5,24(28)-diene-3α,21-diyl disulfate, (20R)-5α-cholestane-3β,21-diyl disulfate, (20R)-3β-hydroxy-5α-cholestan-21-yl sulfate, (20R)-cholest-5-ene-3β,21-diyl disulfate, (20R)-2β-hydroxycholest-5-ene-3α,21-diyl disulfate, (20R)-cholest-5-en-3β-yl sulfate, and (20R)-5α-cholestan-3β-yl sulfate. The first four compounds turned out to be new, whereas the others were identical to the known compounds. Structures of the isolated steroids were identified by two-dimensional NMR spectroscopy and other physicochemical methods. The compounds isolated from starfish are structurally similar to typical ophiuroid metabolites, which support the opinion of some taxonomists that starfish and ophiuroids are phylogenetically related classes.