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.

Pharmacological Study on Antitumor Activity of 5-Fluorouracil-1-Acetic Acid and Its Rare Earth Complexes

The antitumor activity of 5 fluorouracil 1 acetic acid(HFAA) and its lanthanide complexes(La(FAA) 3, Eu(FAA) 3) were studied. The results show that HFAA, La(FAA) 3 and Eu(FAA) 3 with the concentrations of 1 0×10 -5 ～1 0×10 -2 μg·ml -1 inhibit the colony formation of leukemia cells(L 1210 ) and the growth of transplanted tumor sarcoma 180(S 180 ), hepatic carcinoma(HEPA) and ehrlich ascites tumor(EC) as well. The maximum inhibitory rate of Eu(FAA) 3 for S 180 is 38 4%, that HFAA and La(FAA) 3 for EC are 22 4% and 43 4%, respectively. The life prolongation rate of Eu(FAA) 3 for HEPA bearing mice is as long as 284%.

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,Characterization and Antitumor Activity in Vitro of Cd(Ⅲ)Complex with Chelidamic Acid

A novel complex [Cd4（HCAM）4（H2O）8] of Cd（Ⅲ） withchelidamic acid （H3CAM） was synthesized by the hydrothermal method and characterized with IR and emission spectra.The crystal structure was determined based on single-crystal X-ray diffraction data.It crystallizes in monoclinic,space group C2/c with a=17.538（5）,b=12.916（4）,c=16.505（7）,β=100.690（14）o,V=3674（2） 3,Z=8,C14 H14 Cd2N2O14,Mr=659.07,Dc=2.383 g/cm 3,μ=2.400 mm-1,S=1.000,F（000）=2560,the final R=0.0242 and wR=0.0581 for 3656 observed reflections with I〉2σ（I）.The inhibition of the complex against K562 and HL60 cells was determined by MTT assay.The results showed that the concentration of complex was positively correlated with inhibitions against K562 and HL60 cell lines,but inhibitory effects are relatively weak.IC 50 concentration of the title complex on K562 and HL60 cells is 15 and 5 μg/mL,respectively.

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,Crystal Structure and Antitumor Activity of a New Indolequinone Derivative of Ursolic Acid

The title compound（C（37）H（48）BrNO5, 6） was synthesized from ursolic acid and its crystal structure was determined by single-crystal X-ray diffraction analysis. The compound is of orthorhombic system, space group P212121 with a = 16.846（3）, b = 18.844（4）, c = 11.262（2）A, Z =4, V = 3575.1（13） A^3, Mr = 666.67, Dc = 1.239 Mg/m^3, S = 1.002, μ = 1.190 mm^-1, F（000） = 1408,the final R = 0.0831 and wR = 0.1459 for 2286 observed reflections（I 〉 2σ（I））. The crystal structure is stabilized by two intermolecular hydrogen bonds（N–H（0A）···O（2） and O（1）–H（1A）···O（3））. In the preliminary antitumor assay, the title compound 6 exhibits potent cytotoxic activity against Hep G2 and SMMC-7721 cells with IC50 values of 1.64 ± 0.21 and 1.22 ± 0.13 μM, respectively.

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.

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 activities of structure-related small molecular compounds of gambogic acid

Through simplifying the complicated skeleton of the natural product gambogic acid, two series derivatives of chromone and xanthone were synthesized and examined for their antitumor activities against several cancer cells in vitro by MTT method. The results showed that appropriate introduction of prenyl group to the small molecular compounds could elevate their antitumor activities. The structure–activities relationship of synthesized compounds certified that the bridgecore in gambogic acid was very important for keeping its antitumor activities.

DNA Binding and Antitumor Activity of a New Fluores cent ProbeEu(Ⅲ)-Complex Containing 4-Methyl-Coumarin Moiety

A new europium(Ⅲ)complex containing(4-Methyl-2-oxo-2 H-chromen-7-yloxy)-acetic acid moiety(CMMC)was synthesized,characterized,and confirmed as antitumor agent and fluorescent probe.The spectroscopic measurements of Eu(Ⅲ)in the presence of CMMC were obtained in different solvents.The results show that the strongest Eu(Ⅲ)emission bands were monitored in iso-propyl alcohol while the weakest Eu(Ⅲ)emission band was observed in acetonitrile.The interaction of Eu(Ⅲ)-(CMMC)2 complex with DNA was monitored using absorption and emission techniques.From fluorescence titration measurements,the binding constants of DNA with Eu(Ⅲ)-(CMMC)_2 complex were found to be 1.04×10~5 L·mol^(-1) in Tris-HCl and 1.17×10~7 L·mol^(-1) in DMSO-Tris-HCl buffer(9∶1 V/V).Hypochromism was observed from the absorption titration experiment which indicates the intercalation of Eu(Ⅲ)-complex between the base pair of DNA.This result further confirmed by fluorescent Ethidium bromide displacement assay.The fluorescence calibration curve was used for the determination of DNA with LOD of 1.2 ng in DMSO-Tris-HCl buffer(9∶1 V/V)and 5 ng in Tris-HCl buffer.The preliminary antitumor investigation shows promising cytotoxicity against MDA-MB-231,MCF-7(mammary cancer),and PC-3(prostate carcinoma)cell lines with IC50 values of 40.63,25.42 and 30.25μmol·L^(-1),respectively.

Crystal Structure, Synthesis and Biological Activity of Ether and Ester <i>Trans</i>-Ferulic Acid Derivatives

The structures of methoxymethyl (E)-3-(4-hydroxy-3-methoxyphenyl)acrylate, 2;(E)-3-(3-methoxy-4-(methoxymethoxy)phenyl)acrylic acid, 3;methyl (E)- 3-(4-(benzyloxy)-3-methoxyphenyl)acrylate, 4;benzyl (E)-3-(4-(benzyloxy)- 3-methoxyphenyl)acrylate, 6;and (E)-3-(4-(benzyloxy)-3-methoxyphenyl)- acrylic acid, 7;were established by spectroscopic and X-ray diffraction studies. Structure 2 is a new com-pound. Compounds with free phenolic hydroxyls v.gr. methyl (E)-3-(4-hydroxy-3-methoxyphenyl)acrylate 1, 2 and ben-zyl(E)-3-(4-hydroxy-3-methoxyphenyl)acrylate 5, showed scavenging free- radical and antioxidant activity while moderate scavenging free-radical was observed in compound 3. Moderate inhibition of lipid peroxidation was observed for 7. Compound 5 exerted significant inhibition of cell growth in PC-3, K562 tumor cell lines and 4 exhibited the largest cytotoxic effect upon the K562 cell line.

UPLC法测定马甲子药材中马甲子素和messagenic acid B

建立UPLC同时测定马甲子药材中马甲子素和messagenic acid B 2种抗肿瘤活性成分的方法。采用Waters ACQUITY UPLC BEH-C18(2.1 mm×50 mm,1.7μm)色谱柱,乙腈-0.1%甲酸溶液流动相梯度洗脱;流量:0.45 m L/min;柱温30℃;检测波长320 nm。结果表明:马甲子素和messagenic acid B分别在0.198 6~3.972μg,0.151 4~3.028μg范围进样量与峰面积呈现良好的线性关系,平均加标回收率分别为99.20%(RSD=1.34%)和99.69%(RSD=0.56%)。该方法能在3.5 min内使马甲子素和messagenic acid B最大程度地分离,相比较HPLC而言,更加快捷、高效。

Pestalotiopsis属真菌来源Ambuic acid类化学物质及其药理活性研究进展

Ambuic acid类化学成分作为一种潜在的生物群体感应剂,是拟盘多毛孢属Pestalotiopsis真菌的一类特征产物,本文综述了2001年到2021年Pestalotiopsis真菌来源的46个Ambuic acid类化学成分及其药理活性的研究进展,以期为Ambuic acid类成分的研究和开发提供参考。

Synthesis of a novel series of amino acid prodrugs based on tegafur and evaluation of their antitumor activity

As an oral chemotherapy prodrug,tegafur,can be converted to 5-fluorouracil,which is activated to kill tumor cells mainly by the inhibition of thymidylate synthase.In the present study,we synthesized 20 new tegafur derivatives containing amino acid ester groups by substitution,hydrolysis,and condensation.Their structures were confirmed by 1H NMR,13C NMR,and H RMS,and their inhibitory effects on tumor cell growth were studied.The results showed that some of the compounds had good anti-tumor activity.

Synthesis, Characterization, and Evaluation of Antitumor Potential in MCF-7 Cells of Ruthenium-Derived Compounds

To synthesize, characterize and evaluate the antitumor potential derived from ruthenium compounds was generated in this study, from the precursor K[RuCl4(bipy)] a route in a simple and reproducible synthesis for a novel compound of coordinating Ru+3 with bipy and L-trip. The spectroscopic characterization in the middle infrared region (FTIR) shows the interactions between Ru-(L-trip), evidenced by the displacement of the carboxylate ion band for higher energies, and also by the displacements of aliphatic amine bands, suggesting that bidentate coordination of the L-trip ligand occurred. Analysis of the results obtained with thermoanalytical techniques showed that the minimum formula of the compound, [RuCl2(bipy)(L-trip)]1/2H2O. Evaluation of the antitumor potential of precursor K[RuCl4(bipy)] showed the toxic effects on MCF-7 cell line, but did not show selectivity and not reached PBMC cells to the same extent. The evaluation of the antitumor potential of the newly synthesized compound, [RuCl2(bipy)(L-trip)], demonstrated that the insertion of an L-tryptophan molecule into the precursor coordination sphere made it selective when compared to PBMC cells, for MCF-7 type tumor cells.

N-异海松酰基-N′-芳杂环基硫脲类衍生物的合成及生物活性

为得到潜在的新型抑菌剂和抗肿瘤药物,笔者以异海松酸为原料,先与草酰氯反应制备得到异海松酰氯,后与硫氰化钾反应生成异海松酰基异硫氰酸酯,在此基础上与不同杂环取代胺反应,设计并合成了10个新型N-异海松酰基-N′-芳杂环基硫脲类衍生物4a~4j,采用傅里叶红外光谱(FT-IR)、氢核磁共振(1H NMR)、碳核磁共振(13C NMR)和质谱(MS)等手段确定了目标化合物的结构,研究了N-异海松酰基-N′-芳杂环基硫脲类衍生物的抑菌及抗肿瘤活性。研究结果表明,大部分N-异海松酰基-N′-芳杂环基硫脲类衍生物对金黄色葡萄球菌都具有良好的抑菌活性,其中化合物4b、4c、4d、4e和4f对金黄色葡萄球菌的最低抑菌质量浓度达到0.98μg/mL,优于对照物青霉素钠,其中化合物4h的最低抑菌质量浓度也达到15.60μg/mL;化合物4i和4j的最低抑菌质量浓度为31.30μg/mL,大部分衍生物对樟子松枯梢病菌和无壳异担子菌无明显的抑菌活性。在浓度为100μmol/L时,部分N-异海松酰基-N′-芳杂环基硫脲类衍生物具有较好的抗肿瘤活性,化合物4f和4g对肝癌细胞的体外抑制率分别为68.59%和82.30%,化合物4g对宫颈癌细胞、前列腺癌细胞和乳腺癌细胞的体外抑制率分别为80.74%、71.21%和62.14%。

含磺酰胺基团氨基甲酸去氢枞醇酯衍生物的合成及体外抗肿瘤活性

去氢枞酸经还原、酯化和氨基化3步反应合成了19个N-(氨基磺酰基)氨基甲酸去氢枞醇酯类化合物(Ⅳa~Ⅳs),经FTIR、^(1)HNMR、^(13)CNMR和ESI-MS对其结构进行了确认。以5-氟尿嘧啶(5-FU)为阳性对照,采用四甲基偶氮唑盐比色法评价了Ⅳa~Ⅳs对T-24、HepG2、MCF-7、MGC-803和Hela 5种肿瘤细胞株的体外抗肿瘤活性。利用Hoechst-33258染色、细胞集落形成、细胞周期分布、细胞凋亡和蛋白质印迹实验探究了N-[(2-溴苯基)氨基磺酰基]氨基甲酸去氢枞醇酯(Ⅳd)初步作用机制。结果表明,部分化合物抗肿瘤活性优于5-FU,其中,化合物Ⅳd对T-24细胞的细胞毒性活性最好,其半抑制浓度为(14.64±0.46)μmol/L,可明显抑制T-24细胞的生长,阻滞其细胞周期于S期(即DNA合成期);Ⅳd通过线粒体介导的内源性Caspase途径,下调抗凋亡蛋白Bcl-2、Caspase3、Caspase9的表达水平,上调促凋亡蛋白Bax、Cleaved Caspase9、Cleaved Caspase9的表达水平,从而诱导和促进T-24发生凋亡。磺酰胺结构的引入能够改善去氢枞酸衍生物的抗肿瘤活性。

齐墩果酸C-3及C-28位衍生物的设计合成及抗肿瘤活性研究

设计及合成一系列新型齐墩果酸衍生物,并对其进行抗肿瘤活性及分子对接研究。以天然产物齐墩果酸为先导化合物,对其C-3羟基和C-28羧基进行结构修饰,合成新型齐墩果酸衍生物;采用MTT法测定化合物对人肺癌细胞(A549)和乳腺癌细胞(MCF-7)的体外抗肿瘤活性;利用计算机辅助药物设计方法分析所合成化合物关键基团与PI3K受体的作用方式。合成了12个未见文献报道的齐墩果酸衍生物,结构均经1HNMR、13 CNMR及MS谱确证。活性测试结果表明,化合物N-[3β-乙酰氧基-齐墩果烷-12-烯-28-酰]-2-氨基乙醇-4-三氟甲基苯甲酸酯(Ⅰ3)、3β-乙酰氧基-齐墩果烷-12-稀-28β-[N-(3-苯甲酰氨基丙基)]甲酰氨基(Ⅱ1)对肿瘤细胞的抑制活性明显高于母体齐墩果酸与阳性对照药Alpelisib相当。经过结构修饰后的齐墩果酸衍生物具有一定的抗肿瘤作用,值得进一步研究。

Synthesis and Antitumor Activity of Novel Coumarin Deriva- tives via a Three-component Reaction in Water

An efficient synthesis of novel coumarin derivatives via a three-component condensation of 4-hydroxycoumarin, aldehydes and aromatic amines catalyzed by sulfonic acid functionalized ionic liquid L-2-（hydroxymethyl）- 1-（4-sulfobutyl）pyrrolidinium hydrogen sulfate （[HYSBPI]·HSO4） is reported. The condensed product was obtained with excellent yields in water under microwave irradiation condition. The antitumor activities of all the synthesized compounds were assessed on two different human cancer cell lines （A-549 and MCF-7）, and the results showed that these compounds had weak-to-good antitumor activities and their IC50 ranged from 0.05 to more than 100 μmol.L-1.

Improved anti-tumor activity and safety profile of a paclitaxel-loaded glycyrrhetinic acid-graft-hyaluronic acid conjugate as a synergistically targeted drug delivery system

The present study was designed to develop and evaluate glycyrrhetinic acid-graft-hyaluronic acid(HGA) conjugate for intravenous paclitaxel(PTX) delivery. Lyophilized PTX-loaded self-assembled HGA nanoparticles(PTX/HGAs) were prepared and characterized by dynamic light scattering measurements. Hemolysis test, intravenous irritation assessment, and in vitro and in vivo pharmacodynamic studies were carried out. B16F10 and HepG2 cells were used in the cell apoptosis analysis. The mouse MDA-MB-231 xenograft model was used for the evaluation of in vivo anticancer activity of the drugs, by the analysis of tumor growth and side effects on other tissues. PTX/HGAs showed high stability and good biocompability. Compared with PTX plus GA plus HA solution, PTX/HGAs displayed obvious superiority in inducing the apoptosis of the cancer cells. Following systemic administration, PTX/HGAs efficiently suppressed tumor growth, with mean tumor inhibition ratio(TIR) being 65.08%, which was significantly higher than that of PTX plus GA plus HA treatment. In conclusion, PTX/HGAs demonstrated inhibitory effects tumor growth without unwanted side effects, suggesting that HGA conjugates hold a great potential as a delivery carrier for cancer chemotherapeutics to improve therapeutic efficacy and minimize adverse effects.