Diterpenoid alkaloids from a Tibetan medicinal plant Aconitum richardsonianum var. pseudosessiliflorum and their cytotoxic activity

The chemical constituents from Aconitum richardsonianum var.pseudosessiliflorum were investigated.The roots of this plant were extracted three times with 90% EtOH at the room temperature.The ethanol extracts were combined and concentrated under reduced pressure to yield residue,which was suspended in water and successively partitioned with chloroform.The chloroform extraction was isolated and purified by silica gel and Sephadex LH-20 column chromatography.Six compounds were isolated and elucidated as delelatine（1）,isodelpheline（2）,3-acetylaconitine（3）,isoatisine（4）,nordhagenine A（5）and yunaconitine（6）.Compounds 1-5 were obtained from Aconitum Brunneum for the first time.Compound（1）showed significant cytotoxic activities（IC50=4.36 μM）against the human tumor cell line P388.

Synthesis, Crystal Structure and Cytotoxic Activity of a Novel Nickel(II) Complex with Schiff Base Derived from Salicylhydrazide

A novel Schiff base complex with π-conjugated system, [Ni（L1）2（py）2] 1 （L1 =（E）-N′-（2,4-dichlorobenzylidene）-2-oxidobenzohydraizide）, was synthesized and characterized by elemental analysis and single-crystal X-ray determination. Complex 1 crystallizes in the monoclinic system, space group P21/n with a = 12.8286（10）, b = 16.3573（13）, c = 19.0206（14） A, β = 108.2920（10）°, V = 3789.6（5）A^3, Z = 4, Mr = 833.17, Dc = 1.460 g/cm^3,/t = 0.843 mm^-1, F（000） = 1704, the final R = 0.0537 and wR = 0.0640 for 3836 observed reflections with I 〉 2σ（I）. In the molecular structure of 1, the Ni^Ⅱ atoms are six-coordinated by two N and two O atoms from two Schiff base ligands （LI） and two N atoms from two pyridine solvent molecules to form a distorted octahedral geometry. The cytotoxic activities of complex 1 have been experimentally studied against a human HeLa cell in vitro.

Synthesis and cytotoxic activity of novel curcumin analogues

Five novel curcumin analogues bearing different substituents at 4-position of phenyl group were synthesized. Their structures were confirmed by NMR and HRMS spectrum. Their cytotoxic activities against six tumor cell lines were tested by the standard MTT assay in vitro. The results indicated that four analogues （1A-1C, 1E） with solubilizing moieties showed selective potent cytotoxicity against HepG2, HeLa and CT26 cell lines, and analogue 1A and 1C exhibited more potent cytotoxicity than curcumin against CT26 cell line. It was suggested that introduction of appropriate substituents to 4-position of phenyl group might be a potential option for structural modification of curcumin.

Synthesis and cytotoxic activity of heterocycle-substituted phthalimide derivatives

A series of heterocycle-substituted phthalimide derivatives were synthesized.Structurally diverse derivatives with heterocyclic rings,including furan,imidazo[1,2-a]pyridine,1,3,4-thiadiazine,imidazo[2,1-b][1,3,4]thiadiazine,pyrazole,1,2,4-triazolo[3,4- b][1,3,4]thiadiazine,thiazole and thiazoline,were obtained by the reactions ofα-bromoketone intermediate with various nucleophiles containing oxygen,nitrogen and sulfur atom.Their cytotoxic activity was also evaluated against five human cancer cell lines in vitro.

Synthesis, Crystal Structure and Cytotoxic Activity of a New NAN-190 Analogue

The NAN-190 analogue 2-(2-(2-(4-(2-methoxyphenyl)piperazin-1-yl)ethoxy)ethyl)isoindoline-1,3-dione(1, C23H27N3O4, Mr = 409.48) was synthesized via a three-step reaction and characterized by 1H NMR, 13 C NMR, ESIMS and single-crystal X-ray diffraction. The crystal belongs to orthorhombic, space group Pna21 with a = 7.6445(15), b = 38.851(8), c = 7.1316(14) A, V = 2118.0(7) A3, Z = 4, Dc = 1.2840 mg/mm3, μ = 0.089 mm-1, F(000) = 872.4, R = 0.0545 and w R = 0.1681. The single-crystal X-ray structural analysis reveals that the piperazine ring in compound 1 presents a stable and minimum energy chair conformation. In addition, the preliminary cytotoxic assay shows that the title compound exhibits strong and selective inhibitory activity against DU145 cells(IC50 = 5.88 ± 1.02 μM).

Synthesis,Crystal Structure and Cytotoxic Activity of a New N-Vinyl-1H-dibenzo[a,c]carbazole Derivative of the Dehydroabietic Acid

The title compound （C29H33NO2, 3） was synthesized and structurally characterized by elemental analysis, IR, MS, 1H- and 13C-NMR and single-crystal X-ray diffraction. The crystal is of monoclinic system, space group P21 with a = 14.428（3）, b = 7.3440（15）, c = 22.768（5） A, β = 95.17（3）°, V = 2402.7（8） A3, Z = 4, Mr = 427.56, Dc = 1.182 g/cm3, F （000） = 920, 2（MoKa） = 0.71073 A,μ = 0.073 mm-1, the final R= 0.0670 and wR= 0.1002 for 2437 reflections with I〉 2σ（I） Two crystallographically independent molecules with different conformations co-exist in the structure. The crystal structure is stabilized by intermolecular C-H…π interactions which make the molecules stack along the b axis. In addition, the preliminary cytotoxic assay showed that the title compound exhibited moderate inhibitory activity against KB and SW1116 cells.

Isolation, distribution and evaluation of cytotoxic and antioxidant activity of cultivable actinobacteria from the Oman Sea sediments

Screening bioactive natural products from bacteria is a determinative step in the drug discovery programs. The present study aim to isolate actinobacteria from the Oman Sea sediments for determining the effects of different culture media and treatments on the yield of the isolation process, and measure the DPPH radical scavenging and Artemia cytotoxic activity of culture extracts of the actinobacterial isolates. A total of 290 actinobacterial isolates were collected from 14 sediment samples. Heat treatment(40.68%) and M4 medium(29.31%) exhibited the maximum isolation rates of actinobacteria. Streptomyces isolates were dominantly distributed in all of the investigated stations according to 16 S rRNA gene sequencing. The distribution pattern of Streptomyces followed a depth-dependent frequency trend, whereas the members of rare genera including Micromonospora, Nocardia Actinoplanes, Nocardiopsis, Saccharopolyspora and Crossiella were distributed in deeper stations. Approximately,25% of the examined isolates could scavenge 90% of 10^–4 mol/L DPPH solutions at 1 250 μg/mL final concentration of their ethyl acetate culture extracts. Furthermore, the most potent extracts could scavenge DPPH radicals with IC50 ranges from 356.8 to 566.4 μg/mL. Brine shrimp cytotoxicity tests showed that 38.88% of the examined culture extracts exhibited LC50 lower than 1 000 μg/mL against the Artemia cells. Moreover, the most potent culture extracts exhibited LC50 range from 335.4 to 534.4 μg/mL. Phylogenetic analysis by 16 S rRNA gene sequence revealed that the OS 005, OS 263 and OS 157 closely related to Streptomyces djakartensis, Streptomyces olivaceus and Nocardiopsis dassonvillei respectively. These results suggested the widespread distribution of the antioxidant and cytotoxic producing actinobacteria in the Oman Sea sediments, which could be considered as promising candidates for the discovery of microbial bioactive compounds.

Synthesis,Crystal Structure and Cytotoxic Activity of a Zinc(Ⅱ) Complex of the Schiff Base Derived from S-benzyldithiocarbazate

A novel zinc（Ⅱ） complex of empirical formula,ZnL2（L=anionic forms of S-benzyl-β-N-（2,4-dichlorobenzylidene） hydrazine carbodithioate）,has been synthesized and characterized by elemental analysis,IR spectra and single-crystal X-ray diffraction.The crystal belongs to the triclinic system,space group P with a = 9.3168（9）,b = 13.0353（13）,c = 14.7702（15） ,α = 71.2860（10）,= 87.5140（10）,γ = 79.4480（10）o,V = 1670.0（3） 3,Z = 2,Mr = 773.93,Dc = 1.539 g/cm3,μ = 1.334 mm-1,F（000） = 784,the final R = 0.0403 and wR = 0.0800 for 4060 observed reflections with I〉2（I）.In the crystal structure,the zinc（Ⅱ） complex has a distorted tetrahedral geometry in which the zinc ion is coordinated by the nitrogen and sulfur atoms from two Schiff base ligands,respectively.The preliminary bioassay indicates that the Schiff base and its zinc complex exhibit inhibitory activity against the human gastric cancer cell lines（MKN45） and hepatoma cell lines（HepG2）.

Cytotoxic Activity of Betulinic Acid Derivatives Synthesized Using Enzymes

Betulinic acid, a triterpenoid found in many plant species, has attracted attention due to its important pharmacological properties, such as anti-cancer and anti-HIV activities. In order to obtain derivatives potentially useful for detailed pharmacological studies, betulinic acid derivatives were synthesized by reaction of betulinic acid with benzoyl chloride and with acetic anhydride using lipase as catalyst. Enzyme-catalyzed of betulinic acid with benzoyl chloride converted betulinic acid into 3β-benzoil-lup-20（29）-ene-28-oic acid ester （BCL） whereas with acetic anhydride converted betulinic acid into 3β-acetoxy-lup-20（29）-ene-28-oic acid ester （BAA）. The BAA then underwent further reaction with l-decanol to produce 3β-acetoxy-lup-20（29）-ene-28 decanoate （BAAD）. Betulinic acid derivatives prepared were tested for cytotoxic activity on three cancer cell lines in vitro： all tested compounds showed stronger cytotoxic activity than betulinic acid,

Histone Deacetylation Modifier Induced One New Resorcylic Acid Lactone 7′(Z)-zeaenol from the Zoanthid-Derived Fungus Cochliobolus lunatus

Chemical epigenetic manipulation was applied to the zoanthid-derived fungus Cochliobolus lunatus(TA26-46)with a histone deacetylation modifier(100μmol L^(−1) nicotinamide),resulting in the isolation of a new 14-membered resorcylic acid lactone named 7′(Z)-zeaenol(1),together with six known analogues(2−7)from the treated broth.The planar structure of 1 was determined by comprehensive NMR spectroscopy and HRESIMS data.The absolute configuration of 1 was elucidated by ECD spectrum,^(13)C NMR shift calculations,and on the basis of biogenetic considerations.Compound 5 exhibited cytotoxic activity against the human tumor cell lines A549,HCT-116,HT-29,Hela,MCF-7,and K562 with the IC_(50) values ranging from 2.54 to 7.44μmolL^(−1).

Rearranged 19-nor-7,8-seco-labdane diterpenoids and Diels-Alder cycloadducts from the Chinese liverwort Pallavicinia ambigua:Structural elucidation,photoinduced rearrangement,and cytotoxic activity

Two distinctive rearranged 19-nor-7,8-seco-labdane diterpenoids(1 and 2)with a novel tetracyclo[5.2.1.0^(2,5.)0^(4,10)]decane skeleton,a derivative of the open tetrahydrofuran ring(7),three dimeric compounds(8-10),and four revised homologs(3-6)were obtained from Chinese liverwort Pallavicinia ambigua.Their structures were identified via combined analysis of their spectroscopic data,single-crystal X-ray diffraction patterns,and ECD calculations.The light-driven conversion of compound 5 to compounds 1-4 demonstrated that photochemically induced postmodification involved in biosynthesis is an important way to diversify natural structures.A preliminary cytotoxicity assay revealed that compound 5 showed significant inhibition in the human prostate cancer(PC-3)cell line via an apoptotic pathway.

Citrinsorbicillin A,a novel homotrimeric sorbicillinoid isolated by LC-MS-guided with cytotoxic activity from the fungus Trichoderma citrinoviride HT-9

Citrinsorbicillin A(1),a novel homotrimeric sorbicillinoid,along with two new monomers citrinsor-bicillins B(2)and C(3),were isolated from the Coptis chinensis endophyte Trichoderma citrinoviride HT-9 by liquid chromatograph mass spectrometer(LC-MS)-guided strategy.1 was the first trimeric-example from terrestrial fungi,which possessed a unique carbon skeleton with two bicyclo[2.2.2]octanedione ring connected through an enolated carbon forming by[4+2]cycloaddition.Their structures were elucidated by spectroscopic analysis and X-ray diffraction.1 exhibited moderate cytotoxicity against human colon cancer HT29 cells,and it induced significant cell cycle arrest by reducing the protein expression of cyclin D1.

Study on Flavonoids from the Methanol Extracts of Tephrosia purpurea Leaves

[Objective] The aim was to determine flavonoids from the MeOH extracts of Tephrosia purpurea leaves and their cytotoxicitives against the ovarian cells from Sprodenia litura （SL cells）.[Method] The compounds were isolated with column chromatography and their structures were established on the basis of various spectroscopic analysis （including UV,1D and 2D NMR analyses as well as HR-ESRMS）.The cytotoxicity against the SL cells was evaluated by using MTT method.[Result] Six known flavonoids,6-methoxykaempferol （1）,6-methoxykaempferol 7-O-α-rhamnopyranoside （2）,6-methoxykaempferol 3-O-α-rhamnopyranosyl（1→2）[α-rhamno-pyranosyl（1→6）]-β-galactopyranoside （3）,6-methoxykaempferol 3-O-α-rhamnopyranosyl （1 →2）[α-rhamnopyranosyl （1 →6）]-β-galactopyranoside-7-O-α-rhamnopyranoside （4）,pongachin （5）,5,7-dimethoxy-8-（3-hydroxy-3-methylbut-1Z-enyl） flavanone （6） were isolated and determined.Except compound 5,the others were isolated from T.purpurea for the first time.For the cytotoxicity compound 5 had significant activity with the IC50 value of 4.4 mg/L while compound 1 and 3,whose cytotoxicity exceeded rotenone,also showed moderate activity.[Conclusion] Of all the compounds from T.purpurea leaves,the content of 6-methoxykaempferol compounds was considerable.The profiles of these compounds against SL cells suggested that compounds 1,3 and 5,whose cytotoxicity exceeded rotenone,were worth further research.

Synthesis and Antitumor Activities of 26-O-tert-Butyldimethylsiliyl Protodisogenyl β-D-Glucopyranoside

New saponin 26-O-tert-butyldimethylsiliyl protodiosgenyl β-D-glucopyranoside 1 was synthesized and its cytotoxicity activity in vitro was evaluated by MTI＇. It showed potent antitumor activity to human cancer cells. E ring and C22-OH play important roles in the antitumor activity of 1. A method to selective removal of acetyl group in the presence of benzoyl group was reported.

Flavonoid triglycosides from the seeds of Camellia oleifera Abel

Two flavonoid triglycosides, kaempferol 3-O-{ β-D-glucopyranosyl-（1→2）-[α-L-rhamnopyranosyl-（1→ 6）]-β-D-glucopyranoside} （1） and kaempferol 3-O-{ β-D-xylopyranosyl-（1 → 2）-[α-L-rhamnopyranosyl-（1→6）]-β-D-glucopyranoside } （2）, were isolated from the seed of Camellia oleifera Abel. The absolute configuration of compound 1 was established on the basis of its X-ray analysis. Their cytotoxic activities and anti-HIV-RT activities were evaluated.

Three New Anthraquinones from Polygonum cillinerve

Three new anthraquinones, emodin-8-β-D-（2＂-O-coumarate）glucoside 1, emodin-8-β-D-（6＇-O-acetyl）glucoside 2 and physicon-8-β-D-（6＇-O-acetyl）glucoside 3, were isolated from the roots of Polygonum cillinerve and their structures were established by spectroscopic methods. The biological activity indicated that compound 1 had the scavenging activity on 1,1-diphenyl-2-picrylhydrazyl （DPPH） radicals （the IC50 = 8.5 μmol/L）, and compound 1-3 showed no activities against HL-60 and BCJC-823 cells by MTT method in vitro.

Eremophilane sesquiterenes from the marine fungus Penicillium sp.BL27-2

Six eremophilane sesquiterpenes were obtained from a marine fungus Penicillium sp. BL27-2. Their structures were elucidated as 3-acetyl-9, 7 （11）-dien-7a-hydroxy-8-oxoeremophilane （1）, 3-acetyl-13-deoxyphomenone （2）, Sporogen-AO 1 （3）, 7-hydro- xypetasol （4）, 8a-hydroxy-13-deo -xyphomenone （5） and 6-dehydropetasol （6） based on detailed NMR analysis. 1 was a new compound and 2 was obtained as a new natural compound. These compounds were assayed for their cytotoxic activity on P388, A549, HL60, BEL7402 and K562 cell lines by the MTT method. The assay results suggested the epoxide rings in eremophilane molecules were essential for their activity, and acetylation could enhance their activity.

A New Enolate Furostanoside from Asparagus Filicinus

A new enolate derivative of furostanol glycoside, named asparagusin A, was isolated from the roots of Asparagus filicinus and established as 3-O-beta-D-xylopyranosyl(1-->4)-beta-D-glucopyranosyl (25S)-furost-20(22)-ene-3 beta, 26-diol 26-O-beta-D-glucopyranoside (1) by spectroscopic and chemical methods. Asparagusin A (1) exhibited a cytotoxic activity effect on PC12 cells.

Antioxidant and Cytotoxic Phenolic Compounds of Areca Nut(Areca catechu)

Areca catechu L.（Palmae）, commonly known as an important economical seed crop, is widely culti- vated in tropical and subtropical areas, including India, Southeast Asia, East Africa and New Guinea. Areca nut（frequently known as betel nut） is the ripe fruit of the tree A. catechu. Areca nut can be chewed and it is a common masticatory in tropical and subtropical countries. It was estimated in the early 1990s that 10% to 20% of the world＇s population chewed betel quid daily. Areca nut is commonly used in folklore medicine for treatment of various diseases such as dyspep sia, constipation, beriberi and oedema.

Chemical constituents, cytotoxic, antifungal and antimicrobial properties of Centaurea diluta Ait. subsp. algeriensis(Coss. & Dur.) Maire

Objective:To investigate the chemical composition of a moderately polar extract(CHC1_3 soluble part of the MeOH-H_2O extract) obtained from the aerial parts(leaves and flowers) of Centaurea diluta Ait.subsp.algeriensis(Coss.& Dur.) Maire,a species endemic to Algeria and Morocco on which no reports are available to date.To evaluate in vitro the cytotoxic,antifungal and antimicrobial activities of this extract and the cytotoxic and antimicrobial activities of its isolated secondary metabolites.Methods:The cytotoxic effects of the extract were investigated on 3 human cancer cell lines i.e.the A549 non-small-cell lung carcinoma(NSCLC),the MCF7 breast adenocarcinoma and the U373 glioblastoma using a MTT colorimetric assay.Biological data allowed to guide the fractionation of the extract by separation and purification on silica gel 60(CC and TLC).The isolated compounds which were characterized by spectral analysis,mainly HR-ESIMS,HR-EIMS,UV and NMR experiments(~1H,^(13)C,COSY,ROESY,HSQC and HMBC) and comparison of their spectroscopic data with those reported in the literature,were evaluated for cytotoxic activities on six cancer cell lines(A549,MCF7,U373,Hs683 human glioma,PC3 human prostate and B16-F10 murine melanoma).The direct and indirect antibacterial and antifungal activities were determined using microdilution methods for the raw extract and TLC-bioautography and microdilution methods against standard and clinical strains for the isolated compounds.Results:The raw extract reduced cell viability with IC_(50)s of 27,25 and 21 μg/mL on A549,MCF7 and U373,respectively.Five secondary metabolites:two phenolic compounds(vanillin 1,paridol 3),a lignan[(-)-arctigenin 2]and two flavonoid aglycones(eupatilin 4 and jaceosidin 5),were then isolated from this extract.Moderate cytotoxic effects were observed for(-)-arctigenin 2(IC_(50)s:28 and 33μM on Hs683 and B16-F10,respectively),eupatilin 4(IC_(50)s:33 and 47 μM on B16-F10 and PC3,respectively) and jaceosidin 5(IC_(50)s:32 and 40 μM on PC3 and B16-F10,respectively).Conclusions:All the isolated compounds were described for the first time from this species.Although inactive against 7 tested microorganisms(fungi,bacteria and yeast,human or plant pathogens),the raw extract was able to potentiate the effect of beta-lactam antibiotics on methicillin-resistant Staphylococcus aureus(MRSA),reducing the minimal inhibitory concentrations(MICs) by a factor of 2-32-fold.No synergy was found between the extract and streptomycin.From the five isolated compounds only jaseosidin 5 showed a moderate antimicrobial activity.