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.

Cytotoxic Cycloartane Triterpenoid Saponins from the Rhizomes of Cimicifuga foetida

To enrich the bioactive cycloartane triterpenoid glycoside named actein and find out more cytotoxic cycloartane triterpenes,a phytochemical study of Cimicifuga foetida was conducted.113 g(0.17%)actein was purified by recrystallization while eight cycloartane-type triterpenes(1-8)were isolated from the mother liquid.The chemical structures of new compounds(1-4)were elucidated by 1D and 2D NMR and HRESIMS spectroscopic analyses.Moreover,new compounds showed moderate and broad-spectrum cytotoxicity against 5 human cancer cell lines with IC_(50) values ranging from 4.02 to 15.80μM.

Cytotoxic triterpenoid saponins from Ardisia pusilla

A new triterpenoid saponin, 3-O-{ β-D-xylopyranosyl-（1 → 2）-β-D-glucopyranosyl-（1 → 4）-[β-D-glucopyranosyl-（1 → 2）]-α- L-arabinopyranosyl}-3β,16α,28α-trihydroxy-13β,28-epoxy-oleanan-30-al （ardipusilloside Ⅲ, 1）, together with two known saponins, ardisiacrispins A （2） and B （3）, were isolated from the whole plants of Ardisia pusilla A. DC. Their structures were elucidated by extensive spectral analysis and chemical evidences. Saponins 1 and 3 exhibited significant cytotoxicity against human glioblastoma U251MG cells.

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.

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 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.

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.

A Cytotoxic Saponin with Two Monoterpenoids from Albizia julibrissin

A new cytotoxic saponin(1). Julibrosides J(27), was isolated from the stem barks of Alibizia. julibrissin by chromatography, and the structure was elucidated as 3-O-beta-D-xylopyranosyl-(1-->2)-beta -D- fucopyranosyl - (1-->6) -beta -D-glucopyranosyl - 21-O-[(6S)-2 -trans-2-hydroxymethyl-6-methyl-6-O- [4-O-((6S)-2-trans-2-hydroxylmethy 6- methyl - 6- hydroxy)-2,7-octadienoyl-beta-D-quinovopy- -ranosyl]-2.7-octadienoyl}- acacic acid- 28 -O-beta-D-glucopranosyl-(1-->3)-[(alpha-L-arabinofuranosyl-(1-->4)]-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyrnosyl ester based on spectral and chemical evidences.

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.

A comparative study of the antioxidant,antimicrobial,cytotoxic and thrombolytic potential of the fruits and leaves of Spondias dulcis

Objective:To investigate the antioxidant,antimicrobial,cytotoxic and thrombolytic property of the fruits and leaves of Spondias dulcis（S.dulcis）.Methods:Methanolic extracts of fruits and leaves of S.dulcis were partitioned with chloroform and dichloromethane.The antioxidant potential of the crude extract and partitioned fractions were evaluated in terms of total phenolic content,total flavonoid content,DPPH radical scavenging potential,reducing potential and total antioxidant capacity by specific standard procedures.The antimicrobial activity was evaluated using disc diffusion method.The cytotoxicity was evaluated by using brine shrimp lethality bioassay and compared with vincristine sulfate.The thrombolytic activity was compared with streptokinase.Results:The methanolic fruit extract exhibited the highest phenolic content,flavonoid content and antioxidant capacity,among the other extracts,with the highest DPPH radical scavenging activity at a concentration of 10μg/mL(IC50:1.91μg/mL)and maximum reducing power at a concentration of 100μg/ml.(EC50:3.58μg/mL).Though all extract showed moderate antimicrobial activity against the bacterial strains,weak or no activity against fungus.The range of LC50value of all extracts was 1.335-14.057μg/mL which was far lower than the cut off index for cytotoxicity.All extracts exhibited statistically significant（P【0.001）thrombolytic activity.Conclusions:Our study suggested that 5.dulcis exhibits antimicrobial activities against a wide variety of strains while it possesses significant antioxidant,cytotoxic and thrombolytic aclivily.

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).

A new compound with cytotoxic activities from the leaves of Panax ginseng C.A. Meyer

A new compound, 3,6,20（S）-trihydroxy- 12,23-epoxydammar-24-ene,6,20-di-O-β-D-glucopyranoside （1）, was isolated from the leaves of Panax ginseng C.A. Meyer, whose structural elucidation was carried out by means of spectral analysis （including IR, HR- FAB-MS and NMR）. This compound showed the moderate cytotoxic activities against U937 and HeLa cells by using the MTT method.

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.

Synthesis,Crystal Structure and Cytotoxic Activities of Oxazolidin-2-one Derivatives

Four cytotoxic oxazolidin-2-one derivatives were prepared from alkynyl alcohol and isocynate with high yields of 83～95%, and their structures were characterized by IR, H-RESI-MS and NMR analysis. Meanwhile, the crystal of （Z）-4-benzylidene-3-ethyl-1-oxa-3-azaspiro[4.4] nonan-2-one （5a） was obtained and determined by X-ray single-crystal diffraction. Crystal data： monoclinic system, space group P121/c1, a = 10.9284（2）, b = 9.47510（10）, c = 14.2510（2） ？, β = 111.917（2）o, V = 1369.01（3） ？3, Z = 4, F（000） = 552.0, Dc = 1.248 Mg/m3, μ = 0.652 mm-1, R = 0.0473 and wR = 0.1207 for 2699 independent reflections （Rint = 0.0206） and 2581 observed ones （I 〉 2σ（I））.

Synthesis,Crystal Structure and Cytotoxic Activities of 1-(Prop-2-yn-1-yl)-7,8-dihydro-1H-benzo[d][1,3]-thiazine-2,5(4H,6H)-dione Derivatives

The important synthetic precursor（Ⅲ）, 1-（prop-2-yn-1-yl）-7,8-dihydro-1Hbenzo[d][1,3]thiazine-2,5（4H,6H）-dione（C（11）H（11）NO2S）, was prepared through a three-component reaction, which was further transferred into cytotoxic triazoles by alkylation and ＂click＂ synthesis in satisfactory yields of 87%^95%. Their structures were characterized by IR, H-RESI-MS and NMR analysis. Meanwhile, the crystal of Ⅲ was obtained and determined by X-ray single-crystal diffraction. Crystal data： orthorhombic system, space group P212121, a = 5.189（4）, b = 8.661（6）, c = 23.498（17） A, V = 1056.2（13） A^3, Z = 4, F（000） = 464, Dc = 1.392 g/cm^3, μ =0.284 mm^-1, R = 0.0637 and wR = 0.1668 for 8182 independent reflections（R（int） = 0.1580） and 2166 observed ones（I 〉 2σ（I））.

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.

New Secodaphnane-Type Alkaloids with Cytotoxic Activities from Daphniphyllum angustifolium Hutch

One new Daphniphyllum alkaloid,daphnioldhanol A(1),together with three known ones,were isolated from the stem part of Daphniphyllum angustifolium Hutch.Their structures were elucidated by spectroscopic methods and comparing with the literature data.Compound 2 is a new natural product,but known by synthesis as a racemate.Compound 1 exhibited week cytotoxic activity against Hela cell line with IC50 of 31.9μM.

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,

Correlation of the Cytotoxic and Antioxidant Activities of Moroccan Pomegranate （Punica Granatum） with Phenolic and Flavonoid Contents

The Pomegranate （Punica Granatum）, which belongs tothe Lythraceae family, has been used for centuries in traditional Greco-Arab and Islamic medicine of its vermifuge properties and also to treat various diseases. The aim of this research was to investigate the cytotoxicity and antioxidant activities of Moroccan Pomegranate （peel, leaves, branches, flowers and corolla）. Further, the biological activities were correlated with phytochemical contents of the plant extracts. Methanolic extract from different parts of Punica Granatum was assessed for its antiproliferative activity in two human cancer （breast and colon） cells lines （MBA-MD 231 and HT-29）, through MTT （3-（4,5-dimethyl-2- thiazolyl）-2,5-diphenyl-2H-tetrazolium bromide） bioassay using cell viability and cytotoxicity indices. DPPH （2,2-diphenyl-l-picrylhydrazyl） assay was conducted to screen the antioxidant property of the extracts together with its phenolic and flavonoids content were evaluated, as well. The methanolic extract ofPunica Granatum （peel, leaves, branches, flowers and corolla） showed the highest antiproliferative activity on MBA-MD 231 （IC50 was 133.53-233.32 μg/mL） and HT-29 （IC50 was 127.58-203.24 μg/mL） cells. Antioxidants contents are distributed as follows： peel 〉 leaf 〉 flower 〉 corolla 〉 branches. The inhibitory activities required for decreasing initial DPPH by 50% are 8.27, 9.9, 10.06, 11.67 and 13.28 μg/mL, respectively. These results are in correlation with polyphenols content from corolla, peel, leaves, flower and branches are 120.7, 115, 96.65, 90.73 and 64.67 mg GAE/g dw （mg gallic acid equivalents per g dry weight） and flavonoids are 188.8, 221.7, 180.2, 193.7 and 158.5 mg QE/g dw （mg quercetin equivalents per g dry weight）. Our results show that the peel, flowers, corolla, leaves and branches of Moroccan Pomegranate may contain a lot of bioactive compounds which are responsible for strong antioxidant and cytotoxicity activities observed here. Our finding indicates the possibility of using the extracts of this plant as source of natural antioxidant and anticancer mainly for its abundant phenolic and flavonoid contents.