A new isoquinoline derivative from the leaves of Magnolia sieboldii K.Koch

Magnoline（1）,a new isoquinoline derivative,was isolated from the leaves of Magnolia sieboldii K.Koch（Magnoliaceae）.Its structure was elucidated on the basis of spectral analysis including 1D,2D NMR and HR-TOF-MS.

Crystal Structure of 3-(4-Methoxyphenyl)-2-(4-methylbenzoyl)-6,7-dihydro-5H-furo[3,2-g]chromene

The crystal structure of 3-（4-methoxyphenyl）-2-（4-methylbenzoyl）-6,7-dihydro-5H-furo[3,2-g]chromene was obtained by X-ray single-crystal diffraction. The molecule is in the triclinic crystal system, space group P1 with a = 11.0745（4）, b = 13.0953（7）, c = 15.8773（8） ？, α = 92.811（4）, β = 104.815（4）, γ = 111.797（4）o, Z = 4, the final R = 0.0567 and w R = 0.1540. X-ray crystal structure data revealed that one asymmetric structure unit of the title compound contained two molecules. The existence of methyl group changed the dihedral angle between furan ring and the phenyl ring at the C2 position of the furo[3,2-g]chromene scaffold as well as the conformation, and had a further influence on the bioactivity of the furo[3,2-g]chromene derivatives.

Synthesis, Crystal Structure and Biological Activity of 6-Arylmethyl-7H-thiazolo[3,2-b]-1,2,4-triazin-7-one Derivatives as Antitumor Agents

In order to explore the novel anti-tumor agents,ten 6-arylmethyl-3-aryl-777-thiazolo[3,2-b],2,4-triazin-7-ones were designed and synthesized,and the structures were characterized by ^1H-NMR,MS,IR and X-ray single-crystal diffraction analysis.The biological activity results showed that the target compounds exhibited certain inhibitory activity of osteosarcoma cells U2OS-EGFP.Compounds 6a,6g and 6j exhibited more than 70%inhibition ratio at the concentration of 50μmol·L^-1,and especially,the IC5o value of compound 6j was 11.58μmol·L^-1.The crystal of 6h was obtained and analyzed;some related weak interactions were discussed.The molecular docking results showed that the target compounds were supposed to be ERK1/2 inhibitors.

Synthesis,Crystal Structure and Biological Activity of 2-[(Pyridin-2-yl)methylthio]-1H-benzimidazole Derivatives

In order to discover the novel anti-tumor agents, a series of 2-[（pyridin-2-yl）methylthio]-1 H-benzimidazole derivatives were designed and synthesized, and the structures were characterized by IR, MS, and proton NMR. 2-[（3,4-Dimethoxypyridin-2-yl）methylthio]-1 Hbenzimidazole was investigated with X-ray crystallography, and the molecule is in orthorhombic system, space group P212121, with a = 9.1828（16）, b = 11.625（2）, c = 13.463（2） ？, Z = 4, R = 0.0231 and wR = 0.0596. The antitumor activities of target compounds were evaluated against human liver cancer cell line HepG2, and human liver normal cell line HL7702 using MTT assay. The target compounds have demonstrated weak or moderate anti-tumor activity against HepG2, while all the target compounds exhibit no cytotoxic effects on HL7702.

Pharmacophore-based design,synthesis,and biological evaluation of novel 3-((3,4-dichlorophenyl)(4-substituted benzyl)amino)propanamides as cholesteryl ester transfer protein(CETP)inhibitors

Cholesteryl ester transfer protein （CETP） is a plasma glycoprotein that plays an important role in decreasing high-density lipoprotein cholesterol （HDL-C） levels and increasing low-density lipoprotein cholesterol （LDL-C） levels. Inhibition of CETP may be a new therapy for treating atherosclerosis. Herein, we report the development of a ligand-based pharmacophore model and pharmacophore-based virtual screening of the ZINC/big-n-greasy database, leading to the identification of compound H-10 as a potential CETP inhibitor in vitro. Based on H-10, a series of 3-（（3,4-dichlorophenyl）（4-substituted benzyl）amino） propanamides were designed, synthesized, and evaluated against CETP. Compound 41 was found to have the best activity, resulting in 85.0% inhibition of CETP at l0 μmol/L.

Design, Synthesis and Biological Activities of N-（Furan-2-ylmethyl）-lH-indole-3-carboxamide Derivatives as Epidemal Growth Factor Receptor Inhibitors and Anticancer Agents

A series ofN-（furan-2-ylmethyl）-lH-indole-3-carboxamide derivatives（6a--6p） was designed and synthe- sized for developing novel indole scaffolds as anticancer agents targeting the epidemal growth factor receptor （EGFR）, and the cytotoxic activities of the target compounds were evaluated against three EGFR high-expressed cancer cell lines[human lung adenocarcinoma cell line（A549）, Henrietta Lacks strain of cancer cell line（HeLa） and human colorectal cancer cell line（SW480）], one EGFR low-expressed cell line（human liver cancer cell line, HepG2） and one human liver normal cell line（HL7702） using 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyl tetrazolium bromide （MTT） assay, Some target compounds exhibited potent anficancer activities against A549, HeLa, SW480 and weak activities on HepG2, which signifies that the target compounds are likely to be EGFR inhibitors as expected. And they showed weak cytotoxic effects on HL7702, which implies the target compounds are probably to be of low toxicity against normal cells. Among them, the target compound 1-ethyl-N-（fttran-2-ylmethyl）-5-{2-{ [2-（2-methoxy- phenoxy）ethyl]amino}-2-oxoethoxy}-2-methyl-1H-indole-3-carboxamide（6p） with 2-{[2-（2-methoxyphenoxy）ethyl]- amino}-2-oxoethoxy group at the C5 position of the N-（furan-2-ylmethyl）-lH-indole-3-carboxamide scaffold exhibited the most potent anticancer activity. Also the binding interaction of the target compound 6p with EGFR was explored by molecular docking. Conclusively, the novel indole scaffold may be beneficial to investigate new anticancer agents for targeting the EGFR.

Design,synthesis and biological evaluation of sulfenimine cephalosporin sulfoxides as β-lactamase inhibitors

A series of sulfenimine cephalosporin sulfoxide derivatives （Ta-v） were designed, synthesized and evaluated for their inhibitory activity against TEM-1 and cephalosporinase in cell-free systems. Some of the tested compounds showed enhanced inhibitory activity against class C β-lactamase cephalospor- inase compared with the tazobactam. The most promising compounds 7c and 7n （IC50 ~ 7.6 and 8.6 μmol/L, respectively） were further investigated in combination with cefradine against a variety of clinical isolated fi-lactamase-producing bacterial strains.

Design,synthesis and biological evaluation of 1,4-dihydrothieno[3′,2′:5,6]thiopyrano[4,3-c]pyrazole-3-carboxylic amide derivatives as potential estrogen receptor antagonists

雌激素受体是为为在 menopausal 女人，骨质疏松症，象乳癌那样的繁殖癌症，子宫的癌症和前列腺癌症的荷尔蒙代替的治疗学的代理人的一个目标。1,4-Dihydrothieno [3,2:5,6 ] thiopyrano [4,3-c ] pyrazole-3-carboxylic 酰胺衍生物被设计，综合并且生物评估同样潜在的雌激素受体对手。

Design, Synthesis and Antitumor Activity of Pyrrolopyrazinone-chalcone Hybrids

A series of pyrrolopyrazinone-chalcone hybrids（12a-12q） was designed,synthesized and screened for their antitumor activity against SKOV-3,A549 and HeLa cell lines in vitro.Compared with the pyrrolopyrazinone（10a） and 5-fluorouracil（5-FU）,nearly all the tested compounds showed significantly-improved antitumor activities.The most promising compounds 12e and 12k（IC50=0.25 and 0.88 μmol/L） respectively show activities of 123and 35 times that of compound 10a（IC50=30.74 μmol/L） against HeLa cell line.The result reveals that the presence of chalcone moiety is beneficial to their activity and selectivity.

A New Homogenizing Technology to Obtain Rosmarinic Acid from Perilla Oil Meal

Objective To optimize the extraction technology of the active component, rosmarinic acid, an ester of caffeic acid and 3,4-dihydroxyphenyllactic acid, in perilla oil meal for the first time by a new homogenizing technology called smashing tissue extraction (STE). Methods Orthogonal design was used to optimize the extraction condition. The content of rosmarinic acid was quantified from the methanol crude extract with the help of HPLC. Results The optimization of STE process to get rosmarinic acid from the perilla oil meal was the ratio of liquid to solid material at 10:1 and the power of extraction at 150 V, extracting twice (2 min for each time). Conclusion STE could be applied to extracting the active ingredients from the oil meals due to its high extraction efficiency. This new homogenizing technology has advantages on saving extraction time, raising extraction efficiency, and maintaining the temperature sensitive constituents.

A New Cucurbitane Triterpene in Acid-treated Ethanol Extract from Momordica charantia

Objective To study the chemical constituents in the acid-hydrolyzed ethanol extract from Momordica charantia.Methods The ethanol extract from M.charantia was hydrolyzed by 36%HCl and the hydrolysate was isolated by silica gel column chromatography and preparative HPLC.The structures of the isolated compounds were identified by spectral analyses,physical constants,and chemical evidences.Results Two cucurbitane triterpenoids were isolated and identified as 5β,19-epoxy-cucurbita-6,22E,24-trien-3β-ol(1)and cucurbita-6,22(E),24-trien-3β-ol-19,5β-olide(2).Conclusion Compound 1 is a new compound.

Optimization of Smashing Tissue Extraction Technology of Schisandra chinensis Fruits by Orthogonal Test

Objective To optimize the extract technology of active lignins from the fruits of Schisandra chinensis. Methods The content of schizandrin, gomisin A, and deoxyschizandrin were selected as standards to evaluate the efficiency of smashing tissue extraction (STE). Solid-liquid ratio, extracting times, ethanol concentration, and extracting time were investigated through orthogonal test. Results The optimized conditions for STE were ten times amount of 80% EtOH, extracting for three times, and 2 min for each time. Conclusion STE could obtain relatively higher yield, simplicity of operation, and benefit for environment protection. It could be better choice for the extraction of S. chinensis.

Antibacterial steroidal alkaloids from Holarrhena antidysenteriaca

Two new steroidal alkaloids, isoconkuressine and N-formylconessimine, together with 6 known steroidal alkaloids including conkuressine, conessine, isoconessimine, conimine, conarrhimine, and funtudienine, were isolated from the seeds of Holarrhena antidysenteriaca Wall.ex A.DC. Their intrinsic antibacterial activities and synergistic effects with penicillin and vancomycin were analyzed in methicillin sensitive staphylococcus aureus(MSSA) and methicillin resistant staphylococcus aureus(MRSA). Two of the steroidal alkaloids including one new compound(N-formylconessimine) showed potential antibacterial activity and possessed synergistic effects with penicillin and vancomycin, respectively.

Two new C_(21) steroidal glycosides isolated from Cynanchum komarovii

The present study was designed to further investigate the C_(21) steroidal glycosides in Cynanchum plants.Two new steroidal glycosides based on a 13,14:14,15-disecopregnane-type aglycone,komaroside P(1) and komaroside Q(2),together with three known compounds(3-5) were isolated from the whole herbs of Cynanchum komarovii.The aglycones of compounds 1 and 2 were two new disecopregnane.Their structures were elucidated on the basis of 1 D,2 D NMR spectroscopic data and acid hydrolysis.All the compounds(1-5) showed potent inhibitory activities against human leukemia cell lines(HL-60) with IC50 values ranging from 16.6 to 26.3 μmol·L^(-1),compared to the positive control 5-fluorouracil(6.4 μmol·L^(-1)).

A novel mitochondria-targeting tetrapeptide for subcellular delivery of nanoparticles

Mitochondrial dysfunction is associated with the emergence of several neurological and cardiovascular diseases. Hence, mitochondria-targeting delivery strategies are highly significant and critically needed. In this study, we developed a small library of peptides simulating the mitochondria-targeting peptide SS-31, a promising tetra-peptide with antioxidant character, and subsequently evaluated the toxicity, antioxidant ability and mitochondrial delivery of nanoparticles. Among the designed peptides, RF-2 (DArg-Dmt-Arg-Phe-NH2) showed controlled toxicity and excellent protection against gentamicin-induced hair cell damage, as compared with SS-31. More importantly, RF-2-modified PLGA nanoparticles demonstrated high colocalization with mitochondria and comparable specific subcellular accumulation, when compared with SS-31. Taken together, the obtained results supported RF-2 as a mitochondriatargeting peptide with high potential as a targeted carrier.

Iridoid glycosides from the roots of Scrophularia ningpoensis Hemsl

Two new iridoid glycosides,named scrophularianoids A（1） and B（2）,were isolated from the roots of Scrophularia ningpoensis.The chemical structures were established on the basis of extensive analyses of spectroscopic data.Compounds 1 and 2 were inactive in our preliminary in vitro myocardial protective bioassay.

Syntheses and Antiproliferative Activities of Novel Diarylthiosemicarbazide Derivatives

A series of novel N-methylpicolinamide-moiety containing diarylthiosemicarbazide derivatives was prepared and evaluated for their in vitro antiproliferative activity against three cancer cell lines（human alveolar epithelial cell A549, human lung cancer cell H460 and human colorectal cancer cell HT-29） by 3-（4,5-dimethyl）thiazolyldiphenyltetrazoliumromide（MTT） assay. Six compounds（Tb--7g） with halogen substituents exhibited preferable cytotoxicity against one or more cell lines in a low micromolar range. Especially, the most promising compound 7g exhibited remarkable antiproliferative activity with the IC50 values of 2.2, 1.8 and 5.2 μmol/L against A549, H460 and HT-29 cell lines respectively, which is comparable to sorafenib.

Synthesis, Characterization and Biological Activity of Tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine Derivatives as Epidermal Growth Factor Receptor Inhibitors

Based on the molecular docking studies, which were performed to position Erlotinib and the target com- pounds into the active site of the epidermal growth factor receptor（EGFR） to determine the probable binding model, a novel series of 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine derivatives as the novel potential EGFR kinase inhibitors was designed and synthesized. The antitumor activity of all the target compounds against human pulmonary carcinoma cell line A549 has been screened. Of all the target compounds, 4-[2-（l-piperidyl）carbonylmethoxyl- phenthio]-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine（Tj） demonstrated the most potent antitumor activity. Several of the target compounds exhibited moderate antitumor activity. The preliminary structure-activity relation- ships of some target compounds were summarized.

SESQUITERPENES FROM CURCUMA PHAEOCAULIS AND THEIR INHIBITORY ACTIVITIES ON NITRIC OXIDE PRODUCTION IN RAW 264.7 CELLS

Curcumfa phaeocaulis Valeton is used in traditional Chinese medicines for the treatment of blood-related disorders such as blood stasis and inflammation.Our previous studies have found that sesquiterpenes were mainly isolated from C.wenyujin and C.phaeocaulis,while diarylheptanoids were the major compounds from C.kwangsiensis.And most of the isolated compounds exhibited remarkable

Macleayine,a new alkaloid from Madeaya cordata

Macleayine （1）, a new natural occurring alkaloid with a unique spiro [furanone-piperidinedione] framework, was isolated from the aerial parts ofMacleaya cordata. Its unusual structure was established by extensive spectroscopic analyses, computer-assisted structure elucidation software （ACD/Structure Elucidator）, quantum chemistry calculations and ECD calculation. The result of virtual molecular docking predicted the compound can enhance the effects of insulin, and may be used to treat tvpe II diabetes.