芹菜素衍生物的合成及抗肿瘤活性研究

以芹菜素为起始原料,在C-5、C-6、C-7、C-4′位置上引入甲基、苄基、乙酰基、对甲苯磺酰基、三异丙基硅烷基等多种单元结构基团,合成了16个芹菜素衍生物,采用CCK-8的方法考察了所合成化合物对人肝癌细胞(Hep3β)、人结肠癌细胞(LOVO)、人肺癌细胞(A549)的抑制作用。结果显示,经过化学修饰后的部分化合物比芹菜素有更强的抗肿瘤活性,其中化合物13对人肺癌细胞(A549)的抑制率超过了顺铂,值得进一步探讨和研究。     

Identification of a new cytotoxic biflavanone from Selaginella doederleinii

A new biflavanone, 2,2',3,3'-tetrahydrorobustaflavone 7,4',7'-trimethyl ether (1) was isolated from the whole plant of Selaginella doederleinii HIERON. (Selaginellaceae) together with the known biflavonoid, robustaflavone 7,4',7'-trimethyl ether (2) as the cytotoxic constituents against the three human cancer cell lines, HCT, NCI-H358, and K562. The structure of the new compound 1 was elucidated by spectral analysis including various 1D- and 2D-NMR experiments.     

Two New Chromone Glycosides from Selaginella uncinata

Two new chromone glycosides,5-hydroxy-2,6,8-trimethylchromon-7-O-β-D-gluco-pyranoside,named uncinoside A;5-acetoxy-2,6,8-trimethylchromone-7-O-β-D-glucopyranoside, named uncinoside B,and a known chromone compound named 8-methyl eugenitol were isolated from Selaginella uncinate. Their structures were elucidated by spectra analysis of FAB-MS,1D NMR and 2D NMR including ^1H NMR,^13C NMR,HMQC,HMBC and single-crystal X-ray diffraction techniques.     

Two new anthraquinone derivatives and one new triarylbenzophenone analog from Selaginella tamariscina

Abstract

Two new anthraquinone derivatives, selaginones A (1) and B (2), and one new triarylbenzophenone analog, selagibenzophenone B (3), were isolated from Selaginella tamariscina (Beauv.) Spring. Their structures were established by 1D-, 2D-NMR and HR-ESI-MS data. Compounds 1 and 2 represent the uncommon examples of aryl substituted anthraquinone derivatives. Especially, compound 2 is a unique anthranone with exceptional structural feature, in which a p-hydroxyphenyl moiety is attached to the C-10 position. Compound 3 is the second naturally occurring triarylbenzophenone and showed moderate activity against SMCC-7721 and MHCC97-H cell lines with IC₅₀ values of 39.8, 51.5 μM respectively.     

New cytotoxic cerebroside from Gynura divaricata

A new cerebroside,gynuraoside(1),was isolated from the aerial parts of Gynura divaricata DC.It was determined to be 1-O-β- D-glucopyranosyl-(2S,3S,4R,10E)-2-[(2′R)-2′-hydroxyldocosanoyl-amino]-10-octadecene-1,3,4-triol on the basis of chemical and spectroscopic evidence.This compound showed strong cytotoxicity against L1210 leukemia cell line in vitro.     

Two new tetralone derivatives from the culture of Xylaria hypoxylon AT-028

Two new tetralone derivatives named xylariol A （1） and B （2） were isolated from the EtOAc extract of the culture broth of Xylaria hypoxylon AT-028 （Xylariaceae）, and their structures were elucidated by MS, 1R, 1D- and 2D-NMR spectra, and by X-ray diffraction analysis. 1 and 2 showed moderate cytotoxic activities against Hep G2 cells in the in vitro cytotoxic assay with IC50 values of 22.3 and 21.2 μg/mL, respectively.     

Clavulazols A and B,Two New Pyrazine Derivatives from Clavularia Viridis

Two new marine pyrazine derivatives, clavulazols A ( 4 ) and B ( 5 ), were isolated from ethyl acetate extract of the soft coral Clavularia viridis collected in Taiwan. The structures were determined on the basis of spectral analysis, especially 2D NMR as well as chemical conversion.     

Antimicrobial activity of cyathane derivatives from Cyathus subglobisporus BCC44381

Six unknown cyathane diterpenes, named cyathinins A – E, and 10-hydroxyerinacine S, were isolated from Cyathus subglobisporus BCC44381 along with six known compounds, striatoid C, striatin C, striatals A, C, D, and glochidone. The chemical structures were determined by means of high resolution mass spectrometry (HRESI-MS) and nuclear magnetic resonance (NMR) spectroscopy. The absolute configurations were confirmed by X-ray diffraction analysis. The isolated active compounds exhibited antimalarial against Plasmodium falciparum (IC₅₀ 0.88–7.51?μM), antibacterial activities against Mycobacterium tuberculosis (MIC 25–50?μg/mL), Gram-positive bacteria of Bacillus cereus and Enterococcus faecium (MIC 0.78–50?μg/mL) and Gram-negative bacteria of Escherichia coli, Acinetobacter baumannii and Klebsiella pneumoniae in a presence of phenylalanine-arginine β-naphthylamide (MIC 3.13–50?μg/mL), antifungal activity against Candida albicans (IC₅₀ 8.6–80.3?μM) activities, and cytotoxic activity against both cancerous (MCF-7, KB, NCI-H187, IC₅₀ 0.36–28.32?μM) and non-cancerous (Vero, IC₅₀ 0.13–91.50?μM) cells.     

Biflavonoids from Selaginella doederleinii as Potential Antitumor Agents for Intervention of Non-Small Cell Lung Cancer

Four new biflavonoids (1–4) were isolated from Selaginella doederleinii together with a known biflavonoid derivative (5). Their structures contained a rare linker of individual flavones to each other by direct C-3-O-C-4′′′ bonds, and were elucidated by extensive spectroscopic data, including HRESIMS, NMR and ECD data. All isolates significantly inhibited the proliferation of NSCLC cells (IC₅₀ = 2.3–8.4 μM) with low toxicity to non-cancer MRC-5 cells, superior to the clinically used drug DDP. Furthermore, the most active compound 3 suppressed XIAP and survivin expression, promoted upregulation of caspase-3/cleaved-caspase-3, as well as induced cell apoptosis and cycle arrest in A549 cells. Together, our findings suggest that 3 may be worth studying further for intervention of NSCLC.     

Design,cytotoxic effects on breast cancer cell line (MDA-MB 231), and molecular docking of some maleimide-benzenesulfonamide derivatives

A group of novel maleimide-benzenesulfonamide derivatives 3a-d was designed and synthesized for their evaluation as a potential anti-breast cancer agent. The structures of these derivatives were confirmed by their ¹H, ¹³C NMR, Mass, FT-IR spectral data, and melting points. The cytotoxic activity (in vitro) of the selected molecules against MDA-MB231 ​cell line was evaluated by MTT method. Among them, compounds 3a and 3d exhibited a significant cytotoxicity with the IC₅₀ value of 1.61 and 1.26 ​μM, respectively, whereas compounds 3b and 3c showed a moderate cytotoxicity with IC₅₀ values of 0.45 and 1.12 ​μM, respectively against MDA-MB231 ​cells. Docking modeling of the synthesized compounds 3a-d into binding sites of human aromatase protein (PDB ID: 4GL7) was performed to investigate if these derivatives possess analogous binding mode to breast cancer proteins. Docking results showed these compounds have efficient interactions such as hydrogen bonding, Van der Waals interactions, and hydrophobic interactions with the active site residues of the aromatase protein (PDB ID: 4GL7). The low binding energies and a number of hydrogen bonding indicated that the maleimide-benzenesulfonamide derivatives might be considered as a promising anti-breast cancer agent with further developments in drug discovery.     

Design and synthesis of novel cytotoxic podophyllotoxin derivatives

<正>In order to investigate the effect of different C4 linkage moieties on the cytotoxicity of podophyllotoxin derivatives,novel 4-Nand 4-C-substituted 4'-O-demethylepipodophyllotoxin derivatives were designed and synthesized.All the compounds were tested against A549 and MCF-7 tumor cells in vitro,and six compounds showed significant cytotoxicity.The most active compound 9f was superior to GL-331,and exhibited potent cytotoxicity with IC_(50) value at 10~(-7) mol/L level.     

Neolignans and Caffeoyl Derivatives from Selaginella moellendorffii

Ten new phenolic compounds including the six neolignans 1 – 3 and 6 – 8 and four caffeoyl derivatives, i.e., myo‐inositol 1‐caffeate ( 9 ), myo‐inositol 6‐caffeate ( 10 ), myo‐inositol 5‐caffeate ( 11 ), and paucine 3′‐β‐D ‐glucopyranoside ( 12 ) were isolated from the whole plants of Selaginella moellendorffii (caffeic acid=3‐(3,4‐dihydroxyphenyl)prop‐2‐enoic acid). Their structures were established by spectroscopic and chemical methods.     

Three New Illudalane Sequiterpenoids from Pteris semipinnata

The chemical investigation of the aerial parts of Pteris semipinnata resulted in the isolation of three illudalane sesquiterpenoids, namely (2R)‐norpterosin B ( 1 ), (2R)‐12‐O‐β‐D ‐glucopyranosylnorpterosin B ( 2 ), and semipterosin A ( 3 ), along with three known compounds. The structures of 1 – 3 were established by spectroscopic methods, including extensive 2D‐NMR and CD analyses.     

New aplysiatoxin derivatives from the Okinawan cyanobacterium Moorea producens

The marine cyanobacterium Moorea producens is a rich source of diverse compounds that possess a variety of biological activities. In the present study, eight new aplysiatoxin derivatives, namely 6, 8–13, and 15, along with aplysiatoxin (1), debromoaplysiatoxin (2), 3-methoxyaplysiatoxin (3), anhydroaplysiatoxin (4), anhydrodebromoaplysiatoxin (5), oscillatoxin B2 (7), and 30-methyloscillatoxin D (14) were isolated and identified from the Okinawan M. producens. In cytotoxicity and diatom growth inhibition tests, the fifteen compounds tested (1–15) showed moderate or no activity at a concentration of 10?μg/mL.     

Lithocarpinols A and B,a pair of diastereomeric antineoplastic tenellone derivatives from the deep-sea derived fungus Phomopsis lithocarpus FS508

Lithocarpinols A(1) and B(2), a pair of tenellone diastereoisomers with novel fused skeleton were isolated from the deep-sea derived fungus Phomopsis lithocarpus FS508. Their structures were elucidated by comprehensive spectroscopic analyses, X-ray diffraction and quantum molecular calculation. Their plausible biogenetic pathway featured an intriguing carbonyl-ene cyclization. Lithocarpinol A exhibited moderate inhibitory effect against HepG-2 and A549 tumor cell lines with IC_(50) values of 9.4 μmol/L and10.9 μmol/L,respectively.     

Analysis of new benzo-di-lactones and quinones from Lysimachia Fordiana Oliv

Four pigments including two new skeleton benzo-di-lactones fordianin A (1) and fordianin B (2), and another two new quinones fordianaquinone A (3) and fordianaquinone B (4) were firstly isolated from the acetone extract of the leaves of Lysimachia fordiana Oliv. Their structures were elucidated on the basis of spectroscopic methods, mainly 1D and 2D NMR. These four new pigments were evaluated for cytotoxicity against the A549 (human lung cancer) and HeLa (human cervical carcinoma) cell lines.     

New transformation pathway and cytotoxic derivatives from the acid hydrolysis of timosaponin B III

Timosaponin B III is a major bioactive steroidal saponin isolated from Anemarrhena asphodeloides Bge. To potentially discover derivatives with better biological activity, timosaponin B III was structurally modified via acid hydrolysis to yield one new (2, timopregnane A I) C₂₁ steroidal glycoside and seven known compounds. Their structures were elucidated on the basis of NMR spectroscopy and mass spectrometry. All eight compounds were evaluated for cytotoxic activity against MCF7, SW480, HepG2, and SGC7901 cell lines in vitro. As a result, compounds 6 and 7 showed significant activity (IC₅₀ 2.94–12.2?μM) against all tested cell lines. Structure–activity relationships of these compounds were investigated and the preliminary conclusions were provided. Moreover, a new transformation pathway was discovered in the acid hydrolysis of timosaponin B III for the first time.     

Aplicyanins A-F, new cytotoxic bromoindole derivatives from the marine tunicate Aplidium cyaneum

Six new bromoindole derivatives, aplicyanins A-F (1-6), have been isolated from the CH₂Cl₂/MeOH extract of the tunicate Aplidium cyaneum collected in Antarctica. Their structures were determined by extensive analysis of their spectroscopic features, particularly 1D and 2D NMR spectra, and comparison with related compounds. Cytotoxic and antimitotic activities were found for compounds 2 and 4-6.     

Dioxyxanthones from Polygala hongkongensis and Their Cytotoxicity

Two new dioxyxanthones, polyhongkongenoxanthones A and B(1 and 2) were isolated from the herbs of Polygala hongkongensis, together with six known xanthones. Their structures were elucidated on the basis of chemical and spectroscopic evidence. The isolates were tested for their cytotoxicity against three tumor cell lines(HepG2, GLC-82 and MCF-7, HepG2=human hepatocellular carcinoma cells; GLC-82=human lung carcinoma cells; MCF-7= human breast carcinoma cells) by MTT assay, among which polyhongkongenoxanthone B(2), 1,7-dihydroxy-2,3- methylenedioxyxanthone(3) and 1,7-dihydroxy-3,4,8-trimethoxyxanthone(6) are potential antitumor candidate due to their significant cytotoxic effects on the three cell lines..