Design,synthesis and biological evaluation of novel arylpiperazine derivatives on human prostate cancer cell lines

A series of novel arylpiperazine derivatives was synthesized. The in vitro cytotoxic activities of all synthesized compounds against three human prostate cancer cell lines(PC-3, LNCa P, and DU145) were evaluated by a CCK-8 assay. Compounds 8, 10, 13, 17 and 20 exhibited strong cytotoxic activities against the tested cancer cell lines(IC_(50)3 μmol/L). In addition, these compounds exhibited weak cytotoxic effects on human epithelial prostate normal cells WPMY-1. The structure–activity relationship(SAR) of these arylpiperazine derivatives was also discussed based on the obtained experimental data.     

双-β-咔啉衍生物的设计、合成及抗肿瘤活性

以去氢骆驼蓬碱为原料, 经过脱甲基、 烷基化等步骤, 合成了一系列双-β-咔啉衍生物. 目标化合物均经核磁共振谱(NMR)和质谱(MS)进行结构确证. 以顺铂为阳性对照药, 采用四甲基偶氮唑盐(MTT)法考察了目标化合物体外抗肿瘤(Bel-7402, 786-0, BGC-823, A375, 769-P和MCF7等6株细胞)活性. 结果表明, 化合物4g和4o与阳性对照药相比具有良好的抗肿瘤活性, 其半抑制浓度(IC₅₀)值均小于10 μmol/L. 初步构效关系研究表明, 当桥链亚甲基数目为8~10, β-咔啉环上9-丁基或9-异丁基取代时, 化合物的抗肿瘤活性较强.     

Paeonenoides D and E: Two New Nortriterpenoids from Paeonia lactiflora and Their Inhibitory Activities on NO Production

Two new nortriterpenoids, paeonenoides D and E ( 1 and 2 , resp.), together with seven known compounds, were isolated from the roots of Paeonia lactiflora. Their structures were elucidated on the basis of spectroscopic evidence. Compounds 1 – 7 were screened for inhibitory effects against NO production in LPS‐induced RAW246.7 macrophages and for cytotoxic activities against HL‐60, Hep‐G2, and SK‐OV‐3 cell lines. Compounds 1 – 3 and 5 – 7 exhibited inhibitory activities with IC₅₀ values in the range of 9.6–32.2 μM . Triterpenoids with an epoxide ring and a free COOH function, 1 – 3 , showed effectively increased activities compared with other pentacyclic triterpenoids. Compounds 1 – 6 showed significant cytotoxic activities against the Hep‐G2 cell line and modest cytotoxic activities against HL‐60 and SK‐OV‐3 cell lines.     

Phytochemical and cytotoxic investigations of Curcuma mangga rhizomes

Investigations on the cytotoxic effects of the crude methanol and fractionated extracts (hexane, ethyl acetate) C. mangga against six human cancer cell lines, namely the hormone-dependent breast cell line (MCF-7), nasopharyngeal epidermoid cell line (KB), lung cell line (A549), cervical cell line (Ca Ski), colon cell lines (HCT 116 and HT-29), and one non-cancer human fibroblast cell line (MRC-5) were conducted using an in-vitro neutral red cytotoxicity assay. The crude methanol and fractionated extracts (hexane and ethyl acetate) displayed good cytotoxic effects against MCF-7, KB, A549, Ca Ski and HT-29 cell lines, but exerted no damage on the MRC-5 line. Chemical investigation from the hexane and ethyl acetate fractions resulted in the isolation of seven pure compounds, namely (E)-labda-8(17),12-dien-15,16-dial (1), (E)-15,16-bisnor-labda-8(17),11-dien-13-on (2), zerumin A (3), β-sitosterol, curcumin, demethoxycurcumin and bis-demethoxycurcumin. Compounds 1 and 3 exhibited high cytotoxic effects against all six selected cancer cell lines, while compounds 2 showed no anti-proliferative activity on the tested cell lines. Compound 1 also demonstrated strong cytotoxicity against the normal cell line MRC-5. This paper reports for the first time the cytotoxic activities of C. mangga extracts on KB, A549, Ca Ski, HT-29 and MRC-5, and the occurrence of compound 2 and 3 in C. mangga.     

双-β-咔啉衍生物的设计、合成及抗肿瘤活性

以去氢骆驼蓬碱为原料,经过脱甲基、烷基化等步骤,合成了一系列双-β-咔啉衍生物.目标化合物均经核磁共振谱(NMR)和质谱(MS)进行结构确证.以顺铂为阳性对照药,采用四甲基偶氮唑盐(MTT)法考察了目标化合物体外抗肿瘤(Bel-7402,786-0,BGC-823,A375,769-P和MCF7等6株细胞)活性.结果表明,化合物4g和4o与阳性对照药相比具有良好的抗肿瘤活性,其半抑制浓度(IC_(50))值均小于10μmol/L.初步构效关系研究表明,当桥链亚甲基数目为8~10,β-咔啉环上9-丁基或9-异丁基取代时,化合物的抗肿瘤活性较强.     

Two novel alkaloids from the stem of Saprosma hainanense and their cytotoxic activities in vitro

Two novel alkaloids, saprosmine A (1) and saprosmine B (2), were isolated from the stem of Saprosma hainanense MERR., along with five known alkaloids: marcanine A (3); cleistopholine (4); 4-methoxycarbonyl-5,10-benzogquinolinequinone (5); liriodenine (6); and quinoline (7). The chemical structures were established on the basis of extensive spectroscopic (IR, 1D-NMR, 2D-NMR, MS) data analysis and by comparison with spectroscopic data reported in the literature. Compounds 1 to 6 were evaluated for in vitro cytotoxic activities against the SPC-A-1 (human lung cancer), BEL-7402 (human hepatocellular carcinoma), SGC-7901 (human gastric cancer), and K-562 (human myelogenous leukaemia) cancer cell lines. Compounds 1 and 2 exhibited weak cytotoxic activities against K-562 cells. Compounds 3 and 5 showed cytotoxic activities against all four cancer cell lines.     

大黄酸-缬氨酸加合物的合成及初步抗肿瘤活性

以大黄酸为原料,经酯化、烷基化、水解及缩合等反应步骤合成了12个大黄酸-缬氨酸加合物.目标化合物经1H NMR,~(13)C NMR和HRMS进行了结构确证.以顺铂和阿霉素为阳性对照药,采用四甲基偶氮唑盐(MTT)法考察了目标化合物的体外抗肿瘤(Hela,MCF-7,HepG2,KB和HEK293T等5株细胞)活性.结果表明,化合物5l显示出较好的抗肿瘤活性,其IC50值在1.6~9.4μmol/L之间.作用机制研究结果表明,化合物5l能够与DNA发生较强的结合作用.     

Two novel prenylated kaempferol derivatives from fresh bud’s fur of Platanus acerifolia and their anti-proliferative activities

Two novel prenylated kaempferol derivatives (1, 2), together with seven known metabolites were isolated from ethanol extract of fresh Platanus acerifolia bud’s fur by multistep chromatographic processing. Structure of compounds 1 and 2 was confirmed by 1D, 2D NMR spectra and HR-ESI-MS. In addition, compound 1 was further analysed by X-ray crystallography. Anti-proliferative activities in vitro against human breast carcinoma (MCF-7) and human hepatocellular carcinoma (Hep-G2) cell lines for compound 1, 2 and 8 were evaluated. Compound 1 exhibited cytotoxic activity towards MCF-7 and Hep-G2 cell lines with the IC₅₀ values 38.2 and 39.5 μM, respectively. Moreover, compound 2 showed weak cytotoxic activities against the two cell lines.     

Flavonoid glycosides from Chromolaena odorata leaves and their in vitro cytotoxic activity

Two new flavonoid glycosides, (1, 2), and eleven known compounds, (3-13), were isolated from from a 70% EtOH extract of the leaves of Chromolaena odorata (Asteraceae). Their structures were elucidated by 1D and 2D NMR spectroscopic interpretation as well as by chemical studies. The newly isolated compounds were tested in vitro for their cytotoxic activities against the LLC and HL-60 cancer cell lines. Compound 1 showed cytotoxicity against LLC and HL-60 cancer cell lines with IC(50) values of 28.2 and 11.6 μM, respectively. Compound 2 exhibited significant cytotoxic activity in the inhibition of HL-60 cancer cell lines with IC(50) value of 10.8 μM.     

Polyketides and Meroterpenoids from Neosartorya glabra

Two new polyketides, neosarphenols A and B ( 1 and 2 , resp.), were isolated from Neosartorya glabra, together with six known polyketides, 3 – 8 , and two meroterpenoids, 9 and 10 . The structures of the new compounds were elucidated by comprehensive spectroscopic analysis, especially by HR‐ESI‐MS and NMR experiments. All compounds were evaluated for their cytotoxic activities against MDA‐MB‐231, MCF‐7, and PANC‐1 tumor cell lines; 1 and 6 exhibited selective and moderate cytotoxicities against PANC‐1 cell line.     

New Triterpenoid Glycosides from the Roots of Camellia oleifera Abel

Five new triterpenoid saponins, oleiferosides I–M ( 1 – 5 , resp.) were isolated from the roots of Camellia oleifera Abel . Their structures were elucidated by a combination of 1D‐ and 2D‐NMR spectroscopy, mass spectrometry, and chemical methods. All the compounds were identified as oleanane‐type saponins with sugar moieties linked to C(3) of the aglycone. In addition, cytotoxic activities of these saponins were evaluated against four human tumor cell lines (A549, B16, BEL‐7402, and MCF‐7) by using the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) in vitro assay. All of the compounds showed significant cytotoxic activities against the tested cell lines.     

Platinum(II) complexes with thiourea derivatives containing oxygen,sulfur or selenium in a heterocyclic ring: computational studies and cytotoxic properties

Platinum(II) complexes with 1-(2-oxolanylmethyl)-2-thiourea, 1-(2-thiolanylmethyl)-2-thiourea and 1-(2-selenolanylmethyl)-2-thiourea were synthesized in order to compare their cytotoxic activities with those of the free thioureas. Their equilibrium geometries and bonding energies in the gas phase and in solution were calculated using density functional theory at the MPW1PW/LanL2DZ level. The IR spectra of the complexes and their free ligands were compared. Stability of the complexes in 0.9% saline aqueous solution was tested by means of HPLC. The cytotoxic activities of the species against five human cell lines were evaluated, as well as the antimicrobial activities against twelve bacterial strains.     

Lignans and Triterpenes from the Root of Pseuderanthemum carruthersii var. atropurpureum

Two new lignans, pseuderesinol (1), pseuderanoside (2) and a new triterpene, pseuderanic acid (3) were isolated from the dried root of Pseuderanthemum carruthersii (SEEM.) GUILL. var. atropurpureum (BULL.) FOSB. (Acanthaceae), together with ten known compounds, including five lignans, (+)-eudesmin (4), (+)-magnolin (5), (+)-syringaresinol (6), (+)-episyringaresinol (7), (+)-1-hydroxysyringaresinol (8) and five triterpenes, squalene (9), oleanolic acid (10), lupeol (11), betulin (12), betulinic acid (13). Their chemical structures were elucidated by 1D- and 2D-NMR, computational quantum chemistry, as well as high resolution-electrospray ionization (HR-ESI)-MS spectroscopic analysis. The acetylcholinesterase inhibition and cytotoxic activities against HeLa and MCF-7 cancer cell lines were evaluated on some purified compounds at the concentration of 100?μg/mL. Pseuderesinol (1) and magnolin (5) exhibited moderate cytotoxic activities against the MCF-7 cancer cell line.     

Design,Synthesis, Biological Evaluation and Silico Prediction of Novel Sinomenine Derivatives

Sinomenine is a morphinan alkaloid with a variety of biological activities. Its derivatives have shown significant cytotoxic activity against different cancer cell lines in many studies. In this study, two series of sinomenine derivatives were designed and synthesized by modifying the active positions C₁ and C₄ on the A ring of sinomenine. Twenty-three compounds were synthesized and characterized by spectroscopy (IR, ¹H-NMR, ¹³C-NMR, and HRMS). They were further evaluated for their cytotoxic activity against five cancer cell lines, MCF-7, Hela, HepG2, SW480 and A549, and a normal cell line, Hek293, using MTT and CCK8 methods. The chlorine-containing compounds exhibited significant cytotoxic activity compared to the nucleus structure of sinomenine. Furthermore, we searched for cancer-related core targets and verified their interaction with derivatives through molecular docking. The chlorine-containing compounds 5g, 5i, 5j, 6a, 6d, 6e, and 6g exhibited the best against four core targets AKT1, EGFR, HARS and KARS. The molecular docking results were consistent with the cytotoxic results. Overall, results indicate that chlorine-containing derivatives might be a promising lead for the development of new anticancer agents.     

Kadsufolins A – D and Related Cytotoxic Lignans from Kadsura oblongifolia

Kadsufolins A–D ( 1 – 4 , resp.), four new dibenzocyclooctane‐type lignans, were isolated from the roots and stems of Kadsura oblongifolia, together with eleven known lignans. Their structures and configurations were elucidated by spectroscopic methods including 2D‐NMR techniques. The compounds were also evaluated for cytotoxic activity against human tumor cell lines A549 (lung carcinoma), DU145 (prostate carcinoma), KB (epidermoid carcinoma of the nasopharynx), and HCT‐8 (ileocecal carcinoma). Kadsufolin A ( 1 ), kadsufolin D ( 4 ), angeloylbinankadsurin A, and heteroclitin B were found to show cytotoxic activities against A549, DU145, KB and HCT‐8 with GI₅₀ values of 5.1–20.0 μg/ml.     

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.     

Rakicidins G - I,cyclic depsipeptides from marine Micromonospora chalcea FIM 02-523

Rakicidins G-I (1–3), three new cyclic depsipeptides including a long aliphatic chain without terminal methyl branching were isolated from culture broth of Micromonospora chalcea FIM 02–523, along with rakicidin E (4). Their structures were elucidated by extensive NMR and HR-ESI-MS analyses. Compounds 1–4 were evaluated for their cytotoxic activities against HCT-8 and PANC-1 human tumor cell lines under the hypoxic and normoxic conditions. They were approximately 18.2–20.3-fold more cytotoxic under hypoxic than under normoxic conditions on PANC-1, and compared with 7.4–8.7-fold more cytotoxic under hypoxic than under normoxic conditions on HCT-8. Meanwhile, compounds 1–3 were also tested inhibitory activities against gram positive anaerobic bacteria and the results exhibited MIC values in the range of 0.125–8?μg/mL.     

Three New Bisabolane Sesquiterpenes from Ligularia songarica

Three new bisabolane sesquiterpenes, songaricalarins F–H ( 1 – 3 , resp.), and five known analogs, 4 – 8 , were isolated from roots and rhizomes of Ligularia songarica. The structures were elucidated by spectroscopic methods, including 2D‐NMR techniques. The isolated compounds were also evaluated for their cytotoxic activities, against human lung carcinoma (A‐549) and human breast adenocarcinoma (MCF‐7) cell lines, and three compounds were found to show moderate cytotoxicities.     

Cytotoxic Amides and Quinolones from Clausena lansium

Two new amides, claulansamides A and B ( 1 and 2 , resp.), together with five known amides, 3 – 7 and six known quinolones, 8 – 13 , were isolated from the stems and roots of Clausena lansium. Their structures were elucidated on the basis of extensive spectroscopic methods. Their absolute configurations were determined by single‐crystal X‐ray diffraction technique, CD, and optical rotation. HPLC Chiral separation of 1 afforded two enantiomers, (+)‐ and (?)‐claulansamide A, respectively. Compounds 9, 12 , and 13 were isolated from the genus Clausena for the first time. All compounds were evaluated for their cytotoxic activities against A549, BGC‐823, and HeLa cancer cell lines. However, only 9 showed cytotoxic activity against A549 cell line with an IC₅₀ value of 46.3 μM , and 11 against BGC‐823 and HeLa cell lines with the IC₅₀ values of 55.0 and 14.7 μM , respectively.     

Synthesis,cytotoxicity and apoptosis-inducing activity of novel 1H-benzo[d]imidazole derivatives of dehydroabietic acid

With the expectation of finding new and effective antitumor drugs, a series of novel N-(1H-benzo[d]imidazole-2-yl)-benzamide/benzenesulfonamide derivatives of dehydroabietic acid were synthesized and evaluated for cytotoxic activity against three human cancer cell lines (MCF-7, HeLa, and HepG2 cells) and one human normal hepatocyte cell line (LO2). As a result, a number of derivatives showed moderate to good antitumor activities. Among them, compound 8h exhibited the most potent activities against three cancer cell lines with IC₅₀ values of 0.87 ± 0.18, 9.39 ± 0.72, and 8.31 ± 0.64 μM, respectively, and was less active to normal hepatocyte LO2 cells. Further mechanism studies revealed that compound 8h could arrest the cell cycle of MCF-7 cells at S phase and induce the apoptosis of MCF-7 cells in ROS-mediated mitochondrial pathway.