STUDIES ON THE SYNTHESIS AND ANTITUMOR ACTIVITY OF AMINO ACID ESTER DERIVATIVES OF BENZISOSELENAZOLONE

This paper reports a simple method for the synthesis of amino acid ester derivatives of benzisoselenazolone.Their anticancer activity is also given.

Synthesis and antitumor activity of heterocyclic acid ester derivatives of 20S-camptothecins

A series of heterocyclic acid esters of camptothecins as new compounds had been synthesized by acylation method, their in vitro and in vivo antitumor activities were evaluated. The cytotoxic results showed that 6 possessed the best efficacy on six human cancer cell lines in the six classes of CPTs＇ derivatives. In vivo testing results indicated that 9 had better antitumor activity against mouse liver carcinoma H22 than topotecan.

Synthesis and Anti-tumor Activity of Novel Glycyrrhetinic Acid Derivatives

Twenty-five derivatives of glycyrrhetinic acid（GA） modified on the A-ring,at C30 and C11 positions were synthesized.Their in vitro cytotoxicity against various cancer cell lines[henrietta lacks strain of cancer cells（HeLa）,human hepatocellular liver carcinoma cells（HepG2） and human gastric carcinoma cells（BGC-823）] was evaluated by standard MTT[3-（4,5-dimethyl-2-thiazol-yl）-2,5-diphenyl-2H-tetrazolium bromide] assay.All the tested derivatives were found to have stronger cell growth inhibitory than their parent compound GA.Among them,compounds 3a,5a,and 8d have similar activity on HeLa cell line,and compound 8a has similar activity on HeLa,HepG2 and BGC-823 cell lines as Gefitinib.

Synthesis and Antitumor Activity of New Derivatives of Podophyllotoxin

A series of analogues of etoposide (VP-16), the C-4 alkylamino-substituted 4'demethyl-epipodophyllotoxins, have been synthesized and studied for their activity to inhibit L1210 and KB cells in vitro. Most new compounds are as active or more active than VP-16 in their inhibition of both L1210 and KB cells.

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.

Synthesis,Crystal Structure and Antitumor Activity of a Novel Zn(Ⅱ)Complex with 2-(Nicotinoyloxy)acetic Acid Ligand

A novel Zn（Ⅱ） complex, [ZnL2（H2O）4]·H2O（1, HL = 2-（nicotinoyloxy）acetic acid）, was synthesized using Zn（OAc）2·2H2O and 2-（nicotinoyloxy）acetic acid as raw materials. Its structure has been elucidated by elemental analysis, IR and single-crystal X-ray diffraction. The structural analysis revealed that complex 1 crystallizes in triclinic, space group P1 and the Zn（Ⅱ） atom is six-coordinated with two N atoms from two different 2-（nicotinoyloxy）acetate anion ligands and four O atoms from coordinated water molecules. Complex 1 forms a 3D network structure by O–H···O hydrogen bonds. The antitumor activities of 2-（nicotinoyloxy）acetic acid ligand and its Zn（Ⅱ） complex were evaluated against human lung adenocarcinoma A549 cells, human hepatoma SMMC-7721 cells and human colon carcinoma Wi Dr cells.

Synthesis and Antibacterial Activity of Urea and Thiourea Derivatives of Anacardic Acid Mixture Isolated from A Natural Product Cashew Nut Shell Liquid (CNSL)

Synthesis and antibacterial activity of some novel urea and thiourea derivatives (8a - 8k, 9a - 9f) of anacardic acid prepared from commercially available anacardic acid which is obtained from natural product Cashew Nut Shell Liquid (CNSL). Compounds (8a - 8k, 9a - 9f) were tested for Gram positive and Gram negative bacterial cultures. Most of the compounds were showed active compared with standard drug ampicilline.

Synthesis and Antibacterial Activity of Urea and hiourea Derivatives at C-8 Alkyl Chain of Anacardic Acid Mixture Isolated from a Natural Product Cashew Nut Shell Liquid (CNSL)

Synthesis and antibacterial activity of some novel urea and thiourea derivatives (7a-7k, 8a-8f) of anacardic acid prepared from commercially available anacardic acid which is obtained from natural product Cashew Nut Shell Liquid (CNSL). Compounds (7a-7k, 8a-8f) were tested for Gram positive and Gram negative bac- terial cultures. Most of the compounds were showed active compared with standard drug ampicilline.

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 Antitumor Activity of a Na(Ⅰ) Coordination Polymer Based on 2-Propyl-4,5-imidazoledicarboxylic Acid and 1,10-Phenanthroline Ligands

A new Na(I) coordination polymer,[Na2(Hpimdc)(H2 pimdc)(phen)2]n(1), has been synthesized by the reaction of NaOH with 2-propyl-4,5-imidazoledicarboxylic acid(H3 pimdc)and 1,10-phenanthroline(phen). The Na(I) coordination polymer 1 was characterized by single-crystal X-ray diffraction analysis and elemental analysis. In 1, the bridged ligand H3 pimdc adopts two modes(singly deprotonated and doubly deprotonated) to coordinate with the Na(I) ion.The Na(1) ion is six-coordinated with three N atoms from a phen ligand and a H2 pimdc ligand,three O atoms from a Hpimdc ligand and two other different H2 pimdc ligands. The Na(2) ion is also six-coordinated with three N atoms from a phen ligand and a Hpimdc ligand, three O atoms from a H2 pimdc ligand and other two different Hpimdc ligands. Complex 1 exhibits a 1 D chain structure built up by μ-H2 pimdc-and μ-Hpimdc2-ligands. The antitumor activities of complex 1 against human SGC7901, A549 and H08910 cells have been tested.

Synthesis and antitumor activity of 6- and 2-(1-acylsulfanylalkyl)-5,8-dimethoxy-1,4-naphthoquinones

Sixteen novel 6- and 2-（1-acylsulfanylalkyl）-5,8-dimethoxy-l,4-naphthoquinones were designed and synthesized. Their cytotoxicities were evaluated in vitro against BEL-7402, HT-29 and SPC-Al cell lines. The pharmacological results showed that most of the prepared compounds displayed the excellent selectivity for HT-29 cell line. Compound lab exhibited the most potent antitumor activity among the tested compounds.

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.

Synthesis, Crystal Structure and Antitumor Activities of 1,2,3,4-Tetrahydroquinoline-2,4-diyl(bisdiphenylphosphine oxide) Derivatives

A novel and efficient Ir-catalyzed 1,4-and 1,2-addition of diphenylphosphine oxide to quinolines was developed to obtain various 1,2,3,4-tetrahydroquinoline-2,4-diyl(bisdiphenylphosphine oxide) derivatives. The structures of these derivatives were characterized by H-RMS and NMR analysis. X-ray crystallography showed that 3 a is in a monoclinic system, space group of P21/c with a = 13.0464(16), b = 12.6244(16), c = 20.210(3)A,β= 105.215(2)o, V =3211.9(7)A^3, Z = 4, F(000)= 1352,μ= 0.42 mm^–1, S = 1.07, the final R = 0.059 and wR = 0.195.The in vitro antitumor activities of target compounds were evaluated by MTT assay against human cancer K562, HL-60, HeLa and BGC-823. The target compounds demonstrated weak or moderate antitumor activity against these cell lines.

Synthesis, Crystal Structure and Antitumor Activities of N,N,1-Triphenyl-1H-benzo[d]imidazol-5-amine Derivatives

In order to discover the novel antitumor agents,a series of N,N,1-triphenyl-1Hbenzo[d]imidazol-5-amine derivatives were designed and synthesized,and the structures were characterized by IR,H-RMS,1H and 13C NMR.X-ray crystallography showed that 4c is in monoclinic system,space group P1 with a=9.209(2),b=9.533(3),c=14.097(3)?,β=102.069(3)°,V=1202.2(5)?3,Z=2,F(000)=528,μ=1.74 mm–1,S=1.024,the final R=0.0448 and wR=0.1109.The in vitro antitumor activities of target compounds were evaluated by MTT assay against human cancer cell lines K562,HL-60,HeLa and BGC-823.The target compounds demonstrated weak or moderate antitumor activities against these cell lines.

STUDIES ON THE SYNTHESIS OF D-GLUCURONIC ACID DERIVATIVES OF 2-BUTOXY-5-FLUORO-3H-4-PYRIMIDONE AND THEIR ANTICANCER ACTIVITIES

2-Butoxy-5-fluoro-3H-4-pyrimidone derivatives of D-glucuronic acid having 0-glycosidic linkage or N-glycosidic linkage were synthesized and their anticancer activity tested.Their structures were confirmed by elementary analysis,IR spectra and ~1HNMR.

Synthesis and in vitro antitumor activity of 1,3,4-thiadiazole derivatives based on benzisoselenazolone

A series of novel 1,3,4-thiadiazole derivatives based on benzisoselenazolone were synthesized and evaluated for their cytotoxicity in vitro against human liver cancer cell SSMC-7721,human breast cancer cell MCF-7 and human lung cancer cell A549 by CCK-8 assay.The results showed mat compounds 7e,7f,7h,7k,71 and 7m displayed good cytotoxicity against MCF-7 cell lines.Compound 71 exhibited the most potent antitumor activities among the tested compounds.

Synthesis of Novel Spin Labeled Daunomycin Derivatives

Three spin labeled daunomycin derivatives 2-4 were synthesized and their biological activities were tested against mouse leukemia L1210 and human liver cancer BEL-7402 cells in vitro.

Synthesis and structure-insecticidal activity relationship of novel phenylpyrazole carboxylic acid derivatives containing fluorine moiety

A series of novel phenylpyrazole carboxylic acid derivatives containing fluorine moiety,i.e.,diamides 11,simple aryl-bearing amides 12 and acylthioureas 14 were successfully synthesized based on the key fluo ro-containing phe nylpyrazole acid intermediate.The new compounds were identified and confirmed by melting point,1H NMR,13C NMR and elemental analysis or HRMS.The bioassay results indicated that some of the compounds possessed excellent insecticidal activities towards oriental armyworm,diamondback moth and corn borer at low concentrations.For examples,compounds 11a,11e-g and 14b exhibited remarkable larvicidal activities with LC50 values of 0.13-0.39 mg/L and 0.0002-0.0014 mg/L against oriental armyworm and diamondback moth,respectively,were comparable with those of the control chlorantraniliprole.Particularly,lie were found superior to chlorantraniliprole in oriental armyworm tests(LC50:0.23 mg/L vs.0.26 mg/L);11a,lie,11f and 14c in diamondback moth tests with LC50 values of 0.0002 mg/L,0.0002 mg/L,0.0008 mg/L and 0.0005 mg/L,respectively,we re more effective than that of chlorantraniliprole.In addition,12 a also showed a promising insecticidal potential and development/optimization advantage.Compounds 11a,lle-g,12a,14b and 14c could be considered as possible new leading structures for further study.The SAR investigation indicated that the compounds with fluorine motif(e.g.,-F,-CF2H,-CF3)held apparently favorable insecticidal potentials,which provided useful guidance for further design/development of new phenylpyrazole-containing agrochemicals.

Drug discovery based on the structure of FKBP12: Design, synthesis and evaluation of L-1,4-thiazane-3-carboxylic acid derivatives as neuroimmunophilin ligands

By choosing neuroimmunophilin FKBP12 as a therapeutical target, we have attempted to discover a new structural drug for treating neurodegenerative disease. This drug should possess neurotrophic activity and not affect the immune system. Based on the crystal structure of FKBP12, FK506 and Calcineurin complex, a series of small organic molecules were designed. These molecules were to have the ability of binding to FKBP12 in a virtual screening. By using a solution parallel synthetic method, these compounds were synthesized. The neuroprotective and neuroregenerative activities of these compounds were evaluated by binding assays, PC12 cells survival and neurite outgrowth model, chick dorsal root ganglion cultures (DRG) and 6-OHDA lesioned mice sympathetic nerve endings model. The evaluation results of these compounds showed that compound N308 has great promise as a candidate for a neuroprotective and neuroregenerative agent.