Design and Synthesis of Novel Celastrol Derivatives as Potential Anticancer Agents against Gastric Cancer Cells.

Gastric cancer (GC) is a common malignant disease worldwide, and finding novel agents and strategies for the treatment of GC are of urgent need. Celastrol (CEL) is a well-known natural product with antineoplastic activity. In this study, pyrazole analogues were introduced at the C-29 position of CEL. A total of 24 new derivatives were designed, synthesized, and evaluated for their mechanism and antitumor activity in vitro and in vivo. Among them, compound 21 exhibited the best activity against BGC-823 cells (IC50 = 0.21 ± 0.01 µM). Further biological studies showed that 21 significantly raised the reactive oxygen species (ROS) levels to activate the apoptotic pathway, causing mitochondrial dysfunction in BGC-823 cells. In addition, 21 also arrested cells in the G2/M phase to induce tumor cell apoptosis. In a nude mouse tumor xenograft model, 21 exhibited a better tumor inhibition rate (89.85%) than CEL (inhibition rate 76.52%). Taken together, the present study has provided an anticancer lead compound candidate, 21, and has revealed that increased ROS generation may be an effective strategy in the treatment of GC.

Identification of anti-inflammatory components in Sinomenii Caulis based on spectrum-effect relationship and chemometric methods.

The present study aimed to identify the anti-inflammatory components in Sinomenii Caulis (SC) based on spectrum-effect relationship and chemometric methods. A phytochemical investigation of SC extract was performed firstly and afforded eleven potential bioactive compounds. The HPLC fingerprints of 19 batches of SC samples were evaluated by the chemometric methods such as similarity analysis (SA) and hierarchical clustering analysis (HCA). The anti-inflammatory effects of these samples were determined by inhibition of Nitric Oxide (NO) production. Partial least squares regression (PLSR) and artificial neural network (ANN) were used to explore the spectrum-effect relationship of SC. The results indicated that there was a close correlation between chemical fingerprint and anti-inflammatory activity of SC, and peaks 8, 9, 12, 13, 14, 16, 19 and 22 might be potential anti-inflammatory compounds in SC. The verification experiments by testing individual compounds and a combination of them indicated that sinomenine (P8), magnoflorine (P13), menisperine (P16) and stepharanine (P19) were the major anti-inflammatory compounds in SC. Collectively, the present study established the spectrum-effect relationship mode of SC and discovered the anti-inflammatory compounds in SC, which could be used for exploration of bioactive components and quality control of herbal medicines.

Neo-clerodane diterpenes and phytoecdysteroids from Ajuga decumbens Thunb. and evaluation of their effects on cytotoxic, superoxide anion generation and elastase release in vitro.

Five novel compounds, including four neoclerodane diterpenoids, named ajugacumbins KN (1-4) along with a phytoecdysterone, named ajugacetalsterone E (5), were isolated from the whole herbs of Ajuga decumbens (Labiatae). Their structures were elucidated on the basis of detailed spectroscopic analysis including IR, HRESIMS, CD, 1D and 2D NMR spectroscopic experiments. Compounds 1-5 were evaluated for their cytotoxic activities and the effects on superoxide anion generation and elastase release in FMLP/CB-induced human neutrophils.

Two new flavans from the roots of Dianella ensifolia (L.) DC.

Two new flavans, named (2S)-2',4'-dihydroxy-7-methoxy-8-methylflavan (1) and (2S)-2'-hydroxy-4',7-dimethoxy-8-methylflavan (2) were isolated from the roots of Dianella ensifolia. Their structures were elucidated by extensive spectroscopic measurements and comparison with data reported in literatures. Compounds 1 and 2 displayed cytotoxic effects against cancer cell lines MDA-MB-231, B16-F10, HCT116 and A549.

Triterpenoid Saponins with Potential Cytotoxic Activities from the Root Bark of Ilex rotunda Thunb.

A new 19-oxo-18,19-seco-ursane-type triterpeonoid saponin, laevigin E (8), together with 17 known compounds (1 - 7 and 9 - 18) were isolated from the root bark of Ilex rotunda Thunb. Their structures were determined by various spectroscopic analysis. Among them, compounds 6, 9, 11, and 18 were isolated from this species for the first time, while compounds 10 and 12 were firstly isolated from the family Aquifoliaceae. Biological activity assay showed that all triterpenoids exhibit moderate cytotoxic activities against MCF7, A549, HeLa and LN229 cell lines. The four triterpenoid saponins (3, 4, 6, and 8) exhibit slightly better activities compared to the four triterpenoid sapogenins (1, 2, 5, and 7). Compound 8 showed the best cytotoxicity against A549, HeLa and LN229 cell lines with IC50 of 17.83, 22.58 and 30.98 µm, respectively.

A new cycloartane-type triterpenoid from the roots of Dianella ensifolia (L.) DC.

A new cycloartane-type triterpenoid, named 22-hydroxy-cyclolaudenol (1), together with two known cycloartane-type triterpenoids were isolated from the roots of Dianella ensifolia. Their structures were determined based on spectroscopic methods, including UV, IR, HR-ESI-MS, NMR and X-ray diffraction. Compound 1 displayed cytotoxic effects against cancer cell lines B16-F10, A549 and MDA-MB-231.

Cytotoxic limonoids from the root bark of Dictamnus angustifolius.

Three novel limonoids, dictangustone G (1), dictangustone H (2), and dictangustone I (3) were isolated from the root bark of Dictamnus angustifolius. Their structures were elucidated on the basis of detailed spectroscopic analysis including UV, IR, HRESIMS, 1D and 2D NMR spectroscopic experiments. Compounds 1-3 were evaluated for their cytotoxic activities using Hela, A549, MCF7, and LN229 cell lines.

Chemical constituents from Agrimonia pilosa Ledeb. and their chemotaxonomic significance.

Phytochemical investigation of the ethanol extract from the whole plant of Agrimonia pilosa led to the isolation of 31 compounds, including 16 flavonoids (1-16), 5 triterpenes (17-21), 1 isocoumarin (22), 5 phenolic acids (23-27), 1 ceramide (28), 2 agrimols (29-30) and 1 fatty acid (31). Their structures were determined by various spectroscopic analyses. Compounds 5, 7 and 20 were firstly isolated from the genus Agrimonia, and compounds 6, 10-11, 15, 26, 28 and 31 were isolated from the family Rosaceae for the first time. Moreover, the chemotaxonomic significance of these compounds was summarised.

Comparative analysis of volatile oils in the stems and roots of Ephedra sinica via GC-MS-based plant metabolomics.

With a great difference in therapeutic effects of Mahuang (MH, the stems of Ephedra sinica) and Mahuanggen (MHG, the roots of Ephedra sinica), chemical differences between MH and MHG should be investigated. In the present study, gas chromatography-mass spectrometry (GC-MS)-based plant metabolomics was employed to compare volatile oil profiles of MH and MHG. The antioxidant activities of volatile oils from MH and MHG were also compared. 32 differential chemical markers were identified according to the variable importance in the projection (VIP) value of orthogonal partial least squares discriminant analysis (OPLS-DA) and P value of Mann-Whitney test. Among them, chemical markers of tetramethylpyrazine (TMP) and α-terpineol were quantified. Their contents were much higher in most MH samples compared with MHG. The antioxidant assay demonstrated that MH had significantly higher free radical-scavenging activity than MHG. Although MH and MHG derived from the same medicinal plant, there was much difference in their volatile oil profiles. MH samples had significantly higher content of two reported pharmacologically important chemical markers of TMP and α-terpineol, which may account for their different antioxidant activities.

Diterpenoids from Saliva plebeia R. Br. and Their Antioxidant and Anti-Inflammatory Activities.

A new skeleton of diterpenoid, 1,2,3,4,4α,9,10,10α-octahydro-(4α-hydroxyymethyl) -1,1-dimethyl-9-(1-methylethyl)-(2S,3S,4αR,9R,10αS)-2,3,5,7-phenanthrenetertrol, named plebeianiol A (1), along with four known diterpenoids (2-5), were isolated from Salvia plebeia R. Br. Their structures were determined on the basis of spectral analysis. In the bioactivity tests, compounds 1, 2 and 5 showed 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activities with IC50 values of 20.0-29.6 µM. In addition, these three compounds had significant inhibitory effects on reactive oxygen species (ROS) production in lipopolysaccharide (LPS)-induced macrophages. Compounds 1-3 inhibited nitric oxide (NO) production in LPS-induced macrophages with IC50 values of 18.0-23.6 µM. These results showed that compounds 1, 2 had significant antioxidant and anti-inflammatory activities and might provide basis for the treatment of diseases associated with oxidative lesions and inflammation.

A new ellagic acid derivative from Polygonum runcinatum.

A new ellagic acid derivative, 3,3'-dimethylellagic acid-4'-O-(6″-galloyl)-ß-D-glucoside, named runcinatside (5), together with four known compounds 3,3'-dimethylellagic acid (1), 3,3',4'-trimethylellagic acid (2), 3,3'-dimethylellagic acid-4'-O-ß-D-glucoside (3) and 3-methylellagic acid-4'-O-α-L-rhamno-pyranoside (4), was isolated from the roots of Polygonum runcinatum Buch.-Ham. ex D.Don Var. sinense Hemsl and the structures of these compounds were established by spectroscopic methods and comparison with previously reported data. All compounds showed antioxidant activities in vitro and compound 5 possessed the highest activity.

A new antioxidant flavone glycoside from Scutellaria baicalensis Georgi.

A new flavone glycoside, wogonin 7-O-ß-D-ethylglucuronide (1), together with a new natural flavone glycoside baicalein 7-O-ß-D-ethylglucuronide (2) and four known analogues, wogonoside (3), wogonin (4), oroxylin A 7-O-ß-D-methylglucuronide (5) and oroxylin A (6), was isolated from the roots of Scutellaria baicalensis Georgi. The structure elucidation of the new compound was primarily based on HR-ESI-MS, 1D and 2D NMR analyses. Compounds 1 and 3 inhibited FeSO4-Cys-induced liver homogenate lipid peroxidation with IC50 at 18.2 µM and 24.9 µM, respectively, and exhibited strong cytoprotective effects against H2O2-induced oxidative damage in human umbilical vein endothelial cells at low concentrations of 10.0 µM and 3.0 µM.

Flavonoids and other constituents from Aletris spicata and their chemotaxonomic significance.

Eleven compounds, including four flavonoids [(2R,3R)-2,3-dihydro-3,5-dihydroxy-7,4'-dimethoxyflavone (1), 5-hydroxy-7,8,4'-trimethoxy-flavone (2), amentoflavone (10) and apigenin (11)], two penylpropanoids [sinapaldehyde (3) and 3-methoxy-4-hydroxy-cinnamic aldehyde (4)], three phenolic acids [4-hydroxyl-3,5-dimethoxy-benzaldehyde (5), 4-hydroxyacetophen-one (6) and p-hydroxybenzaldehyde (7)], one furan derivative [5-hydroxymethyl furfural (8)] and one steroid saponin [ß-sitosterol-3-O-ß-d-glucoside (9)], were isolated and identified from Aletris spicata. Among them, compounds 1-7, 9 and 10 were reported from the genus Aletris for the first time. Furthermore, seven of them (1-6, 10) were obtained from the family Liliaceae for the first time. Chemotaxonomy of the isolated compounds is discussed briefly.

A new quinoline alkaloid from the roots of Dictamnus angustifolius.

AIM: To investigate the quinoline alkaloids from the roots of Dictamnus angustifolius G.Don ex Sweet (Rutaceae). METHOD: The quinoline alkaloids were isolated by various column chromatographic methods and their structures were elucidated on the basis of spectral analysis. RESULTS: A new quinoline alkaloid, 5-methoxylrobustine (1), along with five known quinoline alkaloids were obtained, and their structures were identified as dictamnine (2), robustine (3), isopteleine (4), γ-fagarine (5), and skimmianine (6). Cytotoxicity testing of these alkaloids showed that all of them had weak cytotoxic activities against human breast cancer cells (MCF7). CONCLUSION: Compound 1 is a new quinoline alkaloid. Alkaloid 3 showed stronger anti-proliferation effect than the other alkaloids.

A new taxane diterpenoid from Taxus chinensis var. mairei.

Taxadiene (3), a new taxane diterpenoid with an unusual hydroxy substituting at C-17, and six known compounds including two taxane diterpenoids (1 and 2) and four flavonoids (4-7) were isolated from the whole seedling of the Taxus chinensis var. mairei. Among them, compound 7 was isolated from T. chinensis var. mairei for the first time. Structures of these compounds were elucidated on the basis of spectroscopic data and by comparison with reported literature data.

Caesappin A and B, two novel protosappanins from Caesalpinia sappan L.

Two novel protosappanins, named Caesappin A (1) and B (2), along with three known protosappanins were isolated from Caesalpinia sappan L. Caesappin A is a new type protosappanin with a seven-membered ring fusing an acetal-type section. Compound 4 was isolated from the genus Caesalpinia for the first time. The structures were elucidated on the basis of spectral analysis and the absolute configuration was determined by the ECD experiment coupled with calculated ECD spectra. Their cytotoxic activities were evaluated using MTT assay.

Degraded limonoids and quinoline alkaloids from Dictamnus angustifolius G. Don ex Sweet. and their anti-platelet aggregation activity.

A new degraded limonoid, named isodictamdiol A (1), two known degraded limonoids (2, 3) and a new nature product of quinoline alkaloid (4) along with five known quinoline alkaloids (5-9) were isolated from the root bark of Dictamnus angustifolius G. Don ex Sweet.. Certain useful NMR data were generalized to determine the structures of compounds 1 and 4. The structural elucidation of Compound 4 was first reported herein. Compounds 1-9 showed significant inhibitory effects on platelet aggregation induced by ADP at 250 µM, while Compound 4 showed potent anti-platelet aggregation activity.

Isolation of a strong promoter fragment from endophytic Enterobacter cloacae and verification of its promoter activity when its host strain colonizes banana plants.

To engineer endophytic Enterobacter cloacae as a biocontrol agent against banana fusarium wilt, a promoter-probe plasmid pUCK was constructed to identify a strong promoter to express disease resistance genes. Using a kanamycin resistance gene for selection, 10 fragments with strong promoter activity were identified from the genome of the E. cloacae KKWB-10 strain. The regions of these 10 fragments that were the primary contributors to the promoter function were identified, and their promoter activities were further evaluated using green fluorescent protein (GFP) as a reporter gene. Fragment 132a″ drove the highest level of GFP activity when the bacteria bearing the fragments were cultured in Luria-Bertani and banana stem extract media. The GFP-expressing strain harboring fragment 132a″ (K-pUCK7-132a″-GT) was then inoculated into banana plantlets (about 1 × 10(7) CFU per plant) to verify the activity of fragment 132a″ in planta. Ten days after inoculation, tissue sections of these banana plantlets were observed by laser confocal scanning microscope. Green fluorescence was observed in the tissues of banana plantlets inoculated with K-pUCK7-132a″-GT but not in uninoculated controls. These results suggest that fragment 132a″ possesses strong promoter activity when its host strain colonizes the banana plants and can be used to engineer endophytic E. cloacae KKWB-10 for biocontrol.

Targeted distribution of bacterial magnetosomes isolated from Magnetospirillum gryphiswaldense MSR-1 in healthy Sprague-Dawley rats.

Bacterial magnetosomes (BMs) have drawn great interest as novel magnetic targeted carriers and have been widely used as carriers for enzymes, nucleic acids and antibodies experimentally. However, BMs have rarely been employed as drug carriers in vivo mainly due to the unclear biocompatibility and pharmacokinetics of BMs. In this study, we provided a unique effective method for purification and sterilization of BMs. The BMs obtained exhibited sterility, high purity, narrowed size-distribution, uniformity in morphology, intact membrane and abundant amino groups in BMs membrane. To elucidate the in vivo body distribution of BMs and if BMs displayed any rejection by animals when they are delivered into the vascular system, the BMs were injected into the sublingual vena of Sprague-Dawley (SD) rats and the tissue distribution of BMs in dejecta, urine, serum and main organs was examined. A target distribution of BMs in SD rats was observed. After injected into the sublingual vena, BMs were only found in livers and there was no obvious evidence to indicate the existence of BMs in the dejecta and urine within 72 h following the intravenous administration.

Preparation and anti-tumor efficiency evaluation of doxorubicin-loaded bacterial magnetosomes: magnetic nanoparticles as drug carriers isolated from Magnetospirillum gryphiswaldense.

Bacterial magnetosomes (BMs) are commonly used as vehicles for certain enzymes, nucleic acids and antibodies, although they have never been considered drug carriers. To evaluate the clinical potential of BMs extracted from Magnetospirillum gryphiswaldense in cancer therapy, doxorubicin (DOX) was loaded onto the purified BMs at a ratio of 0.87 +/- 0.08 mg/mg using glutaraldehyde. The DOX-coupled BMs (DBMs) and BMs exhibited uniform sizes and morphology evaluated by TEM. The diameters of DBMs and BMs obtained by AFM were 71.02 +/- 6.73 and 34.93 +/- 8.24 nm, respectively. The DBMs released DOX slowly into serum and maintained at least 80% stability following 48 h of incubation. In vitro cytotoxic tests showed that the DBMs were cytotoxic to HL60 and EMT-6 cells, manifested as inhibition of cell proliferation and suppression in c-myc expression, consistent with DOX. These observations depicted in vitro antitumor property of DBMs similar to DOX. The approach of coupling DOX to magnetosomes may have clinical potential in anti-tumor drug delivery.