Antitumor Activity of the Ganoderma Lucidum Spore Alcohol Extract in Vitro

Several cancer cell lines(epithelioma cells or leukemia cells)from human being or mouse were first used to study the antitumor activity of the Ganoderma lucidum spore alcohol extract(GLSAE)in vitro by the MTT test A comparision was made between the sporodermbroken(SB)and sporoderm nonbroken(SN)GLSAE It was showed that both GLSAE SB and GLSAE SN could inhibit the proliferation of these cancer cells,but the activity of GLSAE SB was much higher than that of GLSAE SN These results suggested that Ganoderma lucidum spore could probably be used for tumor treatment

Synthesis of Aminoglucose Conjugates of 5-Fluorouracil-1-acetic Acid and 5-Fluorouracil-1-propanoic Acid and Their Antitumor Activities

Six aminoglucose conjugates were synthesized by the reaction of aminoglucose with 5-fluorou-racil-1-acetic acid or 5-fluorouracil-1-propanoic acid and confirmed by IR, 1H NMR and elemental analyses. Their antitumor activities against A2780 cells and PC-14 cells were also evaluated.

Antitumor Actinity of Puqietinone,a Novel Alkaloid fromthe Bulbs of Fritillaria puqiensis

从蒲圻贝母中分得的一种新生物碱蒲贝酮碱，按一定剂量灌胃给药，显示了强的抗小鼠艾氏腹水癌（ＥＡＳ，实体型），宫颈癌（Ｕ＿（１４），实体型）及肝癌（ＨｅＰＡ，实体型）的活性。

Synthesis and Antitumor Activity of Podophyllotoxin Analogues

Seven podophyllotoxin analogues were synthesized by condensation of 4′ demethyl epipodophyllotoxin 10 with 5 alkyl 4 amino 3 mercapto 1,2,4 triazoles 9(a g) in the presence of TFA(CF 3COOH). Their antitumor activities were screened in vitro against HL 60 and K 562 cells.

Berberine displays antitumor activity in esophageal cancer cells in vitro

To investigate the effects of berberine on esophageal cancer (EC) cells and its molecular mechanisms. METHODS Human esophageal squamous cell carcinoma cell line KYSE-70 and esophageal adenocarcinoma cell line SKGT4 were used. The effects of berberine on cell proliferation were evaluated using the 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide (MTT) assay. For cell cycle progression, KYSE-70 cells were stained with propidium iodide (PI) staining buffer (10 mg/mL PI and 100 mg/mL RNase A) for 30 min and cell cycle was analyzed using a BD FACSCalibur flow cytometer. For apoptosis assay, cells were stained with an Annexin V-FITC/PI apoptosis detection kit. The rate of apoptotic cells was analyzed using a dual laser flow cytometer and estimated using BD ModFit software. Levels of proteins related to cell cycle and apoptosis were examined by western blotting. RESULTS Berberine treatment resulted in growth inhibition of KYSE-70 and SKGT4 cells in a dose-dependent and time-dependent manner. KYSE-70 cells were more susceptible to the inhibitory activities of berberine than SKGT4 cells were. In KYSE-70 cells treated with 50 mu mol/L berberine for 48 h, the number of cells in G2/M phase (25.94% +/- 5.01%) was significantly higher than that in the control group (9.77% +/- 1.28%, P < 0.01), and berberine treatment resulted in p21 upregulation in KYSE-70 cells. Flow cytometric analyses showed that berberine significantly augmented the KYSE-70 apoptotic population at 12 and 24 h post-treatment, when compared with control cells (0.83% vs 43.78% at 12 h, P < 0.05; 0.15% vs 81.86% at 24 h, P < 0.01), and berberine-induced apoptotic effect was stronger at 24 h compared with 12 h. Western blotting showed that berberine inhibited the phosphorylation of Akt, mammalian target of rapamycin and p70S6K, and enhanced AMP-activated protein kinase phosphorylation in a sustained manner. CONCLUSION Berberine is an inhibitor of human EC cell growth and could be considered as a potential drug for the treatment of EC patients.

Synthesis and antitumor activities of 2-(E)-(4-cyclopentyloxy-3-methoxylbenzylidene)cyclopentanone derivatives

Aim To design and synthesize a series of 2-（E）-（4-cyclopentyloxy-3-methoxylbenzylidene）cyclopentanone derivatives, and to determine their antitumor activities in vitro. Method The target compounds were synthesized. Their antitumor activities were assayed using human hepatic carcinoma ceil line （Bel-7402） and human oral cavity epidermis squamoceilular carcinoma cell line （KB）. Results Five compounds were obtained. Three of them were not reported in the literature and their chemical structures were confirmed by IR, ^1H NMR, MS and elemental analysis. Preliminary screening results showed that compound 5 possessed better biological activity with IC50 1.62 μmol·L^-1 against Bel-7402 and 8.04 μmol·L^-1 against KB, but much weaker than 5- Fluorouracil. Conclusion Mannich base derivatives of 2-（E）-（4-cyclopentyloxy-3-methoxylbenzylidene）cyclopentanone exhibited some antitumor activities.

Arsenic trioxide encapsulated liposomes prepared via copper acetate gradient loading method and its antitumor efficiency

In this study, arsenic trioxide(ATO) was encapsulated in liposomes via copper acetate(Cu(OAc)2) gradients and high entrapment efficiency of over 80% was obtained. The average particle size and the zeta-potential of the liposomes were detected to be 115.1 ± 29.1 nm and-21.97 ± 0.6 m V, respectively. The TEM images showed rod-like precipitates in the inner aqueous phase, which was supposed be due to the formation of insoluble ATO–Cu complex.The in vitro drug release of ATO–Cu liposomes exhibited a sustained release over 72 h, and the release rates decreased with the increase of the p H of release media. Pharmacokinetic and tissue distribution studies of ATO liposomes showed significantly reduced plasma clearance rate, increased AUC0–12h and T1/2, and improved tumor distribution of As compared to iv administration of ATO solution. The anti-tumor effect of ATO loaded liposomes to S180 tumor-bearing mice was significantly improved with a tumor inhibition rate of 61.2%,meanwhile the toxicity of encapsulated ATO was greatly decreased. In conclusion, ATO can be effectively encapsulated into liposomes by remote loading method via Cu(OAc)2 gradients;the co-administration of ATO and Cu(Ⅱ) via liposomal formulation may find wide applications in the treatment of various tumors.

SOLUTION PROPERTIES OF ANTITUMOR CARBOXYMETHYLATED DERIVATIVES OF α-(1→3)-D-GLUCAN FROM GANODERMA LUCIDUM

Fractions of a water insoluble α-(1→3)-D-glucan (GL) extracted from Ganoderma lucidum were carboxy-methylated (CM) to obtain water-soluble carboxymethylated derivatives (CM-GL) having a degree of substitution (DS) of0.38～0.51. Weight-average molecular weight M_w and intrinsic viscosity [η] of the samples CM-GL were measured by gelpermeation chromatography combined with laser light scattering (GPC-LLS) and viscometry. The CM-GL exhibits a stifferchain in aqueous solution at 25℃ than the original glucan, The antitumor activities against Ehrlich ascites carcinoma (EAC,5×10~6) of the carboxymethylated derivatives from the α-glucan and curdlan, a β-glucan, are significantly higher than thoseof the original glucans. The effects of the relatively low molecular weight, expanded chains and better water-solubility of theCM-GL on the enhancement of antitumor activity could not be neglected. The chain stiffness decreased speedily withincrease of temperature from 40 to 60℃ or NaOH concentration from 0.1 to 0.4 in the solution, respectively, and the changeof the chain stiffness is reversible.

Structure elucidation,immunomodulatory activity,antitumor activity and its molecular mechanism of a novel polysaccharide from Boletus reticulatus Schaeff

A new water-soluble heteropolysaccharide with a molecular weight of 15 k Da was isolated from the fruiting bodies of Boletus reticulatus Schaeff.Structural characterization results revealed that B.reticulatus Schaeff polysaccharide(BRS-X)had a backbone of 1,6-linkedα-D-galactose and 1,2,6-linkedα-D-galactose which branches were mainly composed of a terminal 4-linkedβ-D-glucose and the ratio of D-galactose and D-glucose was 5:1.Bioactivity assays indicated that BRS-X displayed a strong proliferative activity in T cells and B cells and promoted the secretion of immunoglobulin G(Ig G),Ig E,Ig D and Ig M.In addition,BRS-X could facilitate the proliferation and phagocytosis of RAW264.7 cells and could significantly inhibit the growth of tumors in S180-bearing mice.The results of transcriptome sequencing analysis illustrated that total 46 genes enriched in MAPK and total 34 genes enriched in PI3 K/Akt signaling pathways in BRS-X group.The protein VEGF and VEGFR expression were significantly reduced under the treatment with BRS-X.These findings provide a scientific basis for the edible and medicinal value of BRS-X.

Synthesis, Crystal Structure and Antitumor Activity in Vitro of a New Benzoate Binuclear Cupper(Ⅱ ) Complex

The title compound, [Cu2（C7H5O2）4（C2H6O）2], was synthesized by the reaction of benzoic acid, copper acetate and ethanol in an aqueous solution. Trypan blue dye exclusion method was used in experiment. X-ray single-crystal analysis has revealed that compound 1 （C32H32Cu2O10） crystallizes in the monoclinic system, space group C2/c, Mr = 703.66, a = 47.340（5）, b = 6.6613（4）, c = 22.028（2）A,β = 113.284（4）°, V = 6380.6（10） A^3, Z = 8, Dc= 1.465 g/cm^3, F（000） = 2896,μ = 1.388 mm^-11, the final R = 0.0515 and wR = 0.1172 for 5712 observed reflections with I 〉 2σ（I）. X-ray crystal structure analysis suggests that compound [CH2（C7H5O2）4（C2H6O）2] has a binuclear structure with two Cu（II） atoms coordinated by four benzoate groups and two ethanol molecules. The crystal packing is stabilized by intermolecular O-H...O hydrogen bonds. The compound inhibits the proliferation of K562 cells （chronic myeloid leukemic cells） significantly and dose-dependently in 48 h, and IC50 of K562 is 17.3μg/mL by trypan blue dye exclusion method.

Design,Synthesis and Antitumor Activity of Fluoroquinolone C3 Heterocyclic Bis-oxadiazole Methylsulfide Derivatives Derived from Levofloxacin

To discover an efficient route for the shift from an antibacterial fluoroquinolone to an antitumor one based on the mechanistic similarities between targeting topoisomerases and the eukaryotic ones,two series of the title compounds,C3 bis-oxadiazole methylsulfides 6a―6h and corresponding dimethylpiperazinium iodides 7a―7h derived from levofloxacin 1 were designed and synthesized.Their in vitro antiproliferative activities against Chinese hamster ovary cell line（CHO）,murine leukemia cell line（L1210） and human leukocytoma cell line（HL60） were evaluated by MTT assay,and inhibitory effect on DNA topoisomerase IIα was also measured by means of densitometric assay.

The Antitumor Components from Marine-derived Bacterium Streptoverticillium luteoverticillatum 11014 Ⅱ

Eight known compounds were isolated from a marine-derived bacterium Streptoverticillium luteoverticillatum 11014 using bioassay-guided fractionations. Their structures were identified by spectral analysis as bis （4-hydroxybenzyl） ether （1）, p-hydroxyphenylethyl alcohol （2）, N-（4-hydroxyphenethyl） acetamide （3）, indole-3 carboxylic acid methyl ester （4）, dibenzo[b,e] [1,4]dioxine （5）, thymine （6）, cytosine deoxyribonucleoside （7） and 2, 3-butanediol （8）. These compounds were evaluated for their cytotoxic activities against K562 cell line with the SRB method for the first time. Compounds 2 and 4 showed cytotoxcities with IC50 values of 101.1 and 165.3 μolL^-1, respectively. All compounds were isolated from S. luteoverticillatum 11014 for the first time.

Synthesis,Crystal Structure and Antitumor Activities of(14S)-2,14-diphenyl-6,6a,11,12-tetrahydro-5H,10H,14H-[1,8]naphthyridino[1,2-c]pyrido[3,2,1-ij]quinazoline-3-carbonitrile

The title compound（14 S）-2,14-diphenyl-6,6 a,11,12-tetrahydro-5 H,10 H,14 H-[1,8] naphthyridino[1,2-c]pyrido[3,2,1-ij]quinazoline-3-carbonitrile（C31 H26 N4, Mr = 454.56） has been synthesized with 2-aminonicotinaldehyde and 3-oxo-3-phenylpropanenitrile as starting materials, and its crystal structure was determined by single-crystal X-ray diffraction for the first time. The crystal belongs to the triclinic system, space group P1 with a = 8.5833（8）, b = 11.9168（12）, c = 14.4424（14） ？, α = 84.208（3）o, β = 88.427（3）o, γ = 73.704（3）o, V = 1410.7（2） ？3, Z = 2, F（000） = 480, μ = 0.064 mm–1, S = 0.966, the final R = 0.0484 and wR = 0.1388 for 5041 observed reflections with I 〉 2s（I） and 316 variable parameters. The preliminary biological tests show that the title compound has a good antitumor activity against K562 in vitro.

Synthesis and antitumor activity of novel 10-amino acids ester homocamptothecin analogues

Nine racemic homocamptothecin derivatives were synthesized and in vitro antitumor activities were evaluated by standard MTT method. The results showed that some of the compound had higher antitumor activity than iritecan.

Design,synthesis and antitumor activity of a series of novel coumarin-stilbenes hybrids,the 3-arylcoumarins

A series of novel coumarin-stilbenes hybrids called 3-arylcoumarins were synthesized via Perkin reaction and evaluated as potential antitumor agents.The results showed that some compounds exhibited in vitro activity against KB,KV,MCF-7,MCF-7/ ADR cell lines to some extent.Compound 3a showed remarkable effect against KB tumor cells with an IC50 value of 5.18μmol/L.

Antitumor Activity of Diallyl Sulfide in Two-StageMouse Skin Model of Carcinogenesis

It has been reported that diallyl sulfide (DAS), a sulfur-containing volatile compound in garlic (Allium sativum ), exerts anticarcinogenic activity in various rodent tumor models. In the present study, the antitumor property of DAS was tested in Swiss albino mice in the two steqe initiation-promotion mouse skin carcinogenesis. Skin cancers were initiated topically with a single subcarcinOgenic dose (52μg) of 7, 12-dimethyl benz (a) anthracene (DMBA). Promotion was performed by twice weekly applications of 12-O-tetradecanoyl phorbol-13-acetate (TPA) at a dose of 5μg/animal for 32 weeks. DAS was applied topically (250μg/animal) thrice weekly for 3 weeks for anti-initiating and 1 h prior to each promotion treatment for anti-promoting studies. The results showed that the treatment schedule of DAS can effectively delay the onset of tumorigenesis and reduce the cumulative number of tumors and the average number of tumors per mouse. In groups in which DAS applied prior to initiation or promotion, a significant population of the aniinals remained tumor-free till the termination of experiment. These findings suggest that DAS can effectively inhibit chemically induced mouse skincarcinogenesis.

Synthesis, Characterization and Antitumor Activity of Lanthanum(Ⅲ) Complex with Demethylcantharidate

A novel complex of lanthanum （ Ⅲ ） with demethylcantharidate group （DCA）, Na [ La （DCA） 2 （H2O） ], was synthesized in aqueous solution and characterized by elemental analysis, molar conductance, IR, UV, ^1H-NMR spectra and TG-DTA. The results suggest that lanthanum ion is seven-coordinated. Six oxygen atoms are from carboxyl groups and cyclic ethers of two DCA ligand, and on oxygen is from a H2O. The antitumor activities of the complex against HL-60 human leukemia, BGC-823 human gastric carcinoma, Bel-7402 human hepatic carcinoma, Hela human cervical carcinoma were investigated with MT＇F or SRB assays. Na[La（DCA）2（H2O）] exhibits stronger inhibition against certain kinds of cancer cells than Na2DCA in vitro.

Syntheses, Crystal Structures, and Antitumor Activities of Two 2-Trifluoromethyl-5,6,7,8-tetrahydrobenzo[4,5]-thieno[2,3-d]pyrimidin-4-amine Derivatives

Two novel 2-trifluoromethyl-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-amine derivatives were synthesized by nucleophilic substitution of two appropriate amines with 4-chloro-2-(trifluoromethyl)-5,6,7,8-tetrahydrobenzothieno[2,3-d]pyrimidine, which started from 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile, trifluoroacetic acid(TFA) and phosphorous oxychloride by one-pot procedure. Their structures were determined by single-crystal X-ray diffraction. Compound 1, N-(furan-2-ylmethyl)-2-trifluoromethyl-5,6,7,8-tetrahydrobenzothieno[2,3-d]pyrimidin-4-amine, crystallizes in the monoclinic system, space group C2/c with a = 26.352(3), b = 7.5991(8), c = 17.1423(18) A, β = 114.667(2)°, V = 3119.5(6) A3 and Z = 8. Compound 2, N-(3-silatranylpropyl)-2-trifluoromethyl-5,6,7,8-tetrahydrobenzothieno[2,3-d]pyrimidin-4-amine, crystallizes in the monoclinic system, space group P21/n with a = 13.4394(13), b = 8.9446(9), c = 18.9657(18) A, β = 101.9640(10)°, V = 2230.3(4) A3 and Z = 4. The preliminary bioassay indicated that compound 2 exhibits more potent antitumor activity against BCG-823 than 5-fluorouracil(5-FU).

Crystal Structure and Antitumor Activity of Tri[2- [N-(4'-methyl-benzylsulfonyl)amino]ethyl]-amine

The crystal structure of the title compound (C27H38N4O7S3, Mr = 626.79) has been determined by single-crystal X-ray diffraction. The crystal is of triclinic, space group Pīwith a = 9.411(1), b = 11.645(2), c = 14.672(2) , a = 91.80(1), b = 95.36(1), g =104.56(1)o, V = 1547.0 3, Z = 2, Dc = 1.346 g/cm3, l = 0.71073 , m(MoKa) = 0.289 mm-1 and F(000) = 664. The structure was refined to R = 0.0406 and wR = 0.1177 for 4103 observed reflections with I > 2s(I). X-ray diffraction analysis reveals that the title compound is a practically distorted tetrahedron and each molecule contains one lattice H2O by hydrogen bond. The antitumor activity of the title compound against HL-60 human leukemia cells has also been studied by MTT method.

Synthesis, Crystal Structure and Antitumor Activity of N-[5-(Benzylthio)-1,3,4-thiadiazol-2-yl]-4-chlorobenzamide

The title compound N-[5-（benzylthio）-1,3,4-thiadiazol-2-yl]-4-chlorobenzamide（C（16）H（12）ClN3OS2, Mr = 361.86） was designed and synthesized as anticancer agent, and its crystal structure was determined by single-crystal X-ray diffraction. The crystal belongs to triclinic, space group P1 with a = 5.7417（10）, b = 9.8057（17）, c = 14.330（3） A, a = 91.987（3）, b = 97.154（3）, γ = 93.402（3）°, V = 798.4（2） A3, Z = 2, Dc = 1.505 g/cm^3, μ = 0.507 mm-1） F（000） = 372, the final R = 0.0481 and wR = 0.1290 for 2064 observed reflections with I 〉 2s（I）. In the crystal packing, the molecules form stacks by a three-dimensional framework, which results from intermolecular N（1）-H（1）···N（2） and C（5）-H（5）···N（3） hydrogen bonds together with π-π stacking interactions between the thiadiazole and chlorobenzene rings. The title compound was found to exhibit more potent in vitro antitumor activities against the four tested cancer cell lines than sorafenib.