Secondary Metabolites from the Leaves of Litsea lii var. nunkao‐tahangensis

Investigation of the leaves extract of Litsea lii var. nunkao‐tahangensis led to the isolation of five new butanolides, litsealiicolide A ( 1 ), isolitsealiicolide A ( 2 ), litsealiicolide B ( 3 ), isolitsealiicolide B ( 4 ), and isolitsealiicolide C ( 5 ), along with 17 known compounds. Their structures were determined through in‐depth spectroscopic and mass‐spectrometric analyses. Among the isolates, compounds 1 and 2 were cytotoxic against MCF‐7, NCI‐H460, and SF‐268 cell lines in vitro. Compound 5 and isolinderanolide B ( 6 ) showed marginal cytotoxic activity against these three cell lines in vitro.     

Phragmalin-type limonoid orthoesters from Chukrasia tabularis var. velutina

Nine new phragmalin-type limonoid orthoesters, tabulalides F-N (1-9), together with three known compounds, tabulalides C and D, and tabularisin N (10-12), were isolated from the stem bark of Chukrasia tabularis var. velutina. Extensive spectroscopic technologies were applied to elucidate the structures of these new compounds, including the application of circular dichroism (CD) exciton chirality method for the determination of the absolute configurations of 1 and 2. Tabulalide F (1) has a rare orthoisobutylate moiety in phragmalin-type limonoid orthoesters. These compounds were evaluated for cytotoxic activity against five human cancer cell lines in vitro. Tabulalide G (2) exhibits moderate cytotoxic activity against MCF-7 with IC(50) value of 20.4 μmol/l, and other compounds have weak inhibitory effects on the growth of tested tumor cells.     

Cytotoxic triterpenes from Salvia buchananii roots

A pentacyclic triterpene, named salvibuchanic acid (1), together with five known compounds, were isolated from the roots of Salvia buchananii Hedge (Lamiaceae). The structural characterisation of all compounds was performed by spectroscopic analyses, including 1D and 2D NMR and HRESIMS experiments. The lupane triterpene (1) and hyptadienic acid (2) were investigated for their potential cytotoxic activity on Jurkat, HeLa and MCF7 cell lines. Both compounds showed an interesting antiproliferative activity with similar potency in all cell lines. By means of flow cytometric studies, hyptadienic acid (2) induced in HeLa cells a S cell cycle block, while 1 elicited both cytostatic and cytotoxic responses.     

A novel 18-norclerodane diterpenoid from the roots of Tinospora sagittata var. yunnanensis

A novel 18-nor-clerodane diterpenoid named sagitone (1) was isolated from the 95% ethanol extract of dry roots of Tinospora sagittata var. yunnanensis together with the five known diterpenoids columbin (2), palmatoside C (3), fibleucin (4), tinophylloloside (5) and epitinophylloloside (6). The structure of the new compound 1 was determined based on MS, IR, 1D and 2D NMR spectral data. The compounds 1-6 did not show significant cytotoxic activity against cancer cell lines K562 and HL-60.     

Synthesis and tumor cytotoxicity of novel amide derivatives of β-hederin

Thirteen novel triterpenoid saponins, designed as amide derivatives of the natural cytotoxic saponin β-hederin, were synthesized by a stepwise glycosylation strategy. The in vitro cytotoxic activity of these compounds was evaluated against five different tumor cell lines. Most of the evaluated compounds showed effective inhibitory activity against at least one tumor cell line at micromolar concentrations. The preliminary structure-activity relationships (SAR) indicate that mide derivatization at C-28 resulted in highly cytotoxic derivatives on specific tumor cell lines, and also resulted in an increase in the antitumor selectivity of β-hederin.     

Hyperisampsins N and O,two new benzoylated phloroglucinol derivatives from Hypericum sampsonii

Twenty-one benzoylated phloroglucinol derivatives bearing homoadamantyl frameworks were isolated from the aerial parts of Hypericum sampsonii, including two new ones named hyperisampsins N and O (1 and 2). The structures of 1 and 2 were elucidated by extensive NMR and mass spectrometric analyses. Their absolute configurations were further determined by using TDDFT ECD calculations. Compounds 2, 7, and 8 were evaluated for their cytotoxic activities against five human cancer cell lines, of which, 2 and 8 exhibited significant cytotoxic activities toward HL-60 cell and moderate activities against others cell lines.     

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.     

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.     

Synthesis,Cytotoxic Activity Evaluation of Novel 1,2,3‐Triazole Linked Quinazoline Derivatives

A series of novel 1,2,3‐triazole‐quinazoline derivatives were synthesized in five steps starting from anthranilamide by conventional methods. All the title compounds 10a — 10r were evaluated for cytotoxic activity against four human cancer cell lines (MGC ‐803, EC ‐109, MCF ‐7 and HGC ‐27) using MTT assay in vitro . Some of the synthesized compounds exhibited moderate to potent activity against tested cancer cell lines. Among them, compounds 10 h and 10q exhibited excellent growth inhibition against HGC ‐27 and compound 10 m also possessed excellent activity against MCF ‐7, with IC₅₀ values less than 1 µmol/L. Especially, compound 10 h was more cytotoxic than 5‐fluorouracil against all tested four human cancer cell lines.     

Two New Chemical Constituents of Veratrum dahuricum (Turcz.) Loes. f.

Two new chemical constituents, one new steroid, neoveratrenone ( 1 ), and one new glycerol ester, 1‐[11‐(ferulyloxy)undecanoyl)]glycerol ( 2 ), were isolated and characterized from the roots and rhizomes of Veratrum dahuricum (Turcz .) Loes . f., together with five known compounds, i.e., hexacosanoic acid 2,3‐dihydroxypropyl ester ( 3 ), syringaresinol ( 4 ), prosapogenin A of dioscin ( 5 ), verapatulin ( 6 ), and oxyresveratrol ( 7 ). Their structures were established by extensive analysis of spectroscopic data as well as by comparison with literature reports. The compounds were evaluated for cytotoxic activity against three tumor cell lines of HepG‐2, HeLa, and K562/S.     

Design, synthesis, and biological evaluation of novel spin-labeled derivatives of podophyllotoxin as potential antineoplastic agents. Part XII

Five novel nitroxyl spin-labeled ester derivatives of podophyllotoxin (11a-11e) have been prepared and their structural information on these nitroxyl spin-labeled ester derivatives of podophyllotoxin (11a-11e) using (1)HNMR spectroscopy was efficiently obtained by application of the in situ reduction of representative nitroxyl spin-labeled ester derivative of podophyllotoxin 11e with phenylhydrazine for the preparation of N-hydroxylamine 12 in the NMR tube. These novel derivatives were further evaluated for their in vitro cytotoxic activity against five neoplastic cell lines (K562, HL-60, SPCA-1, Lewis, and L-1210) using MTT assay. Most of the target compounds (except for all these compounds against SPCA-1) exhibited more pronounced cytotoxicity against several neoplastic cell lines than that of the prototypical inhibitor etoposide.     

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.     

Isolation and purification of diterpenoids from the aerial parts of Isodon excisoides target-guided by UPLC-LTQ-Orbitrap-MS

Cytotoxic diterpenoids were enriched and orientation prepared from the aerial parts of Isodon excisoides target-guided by UPLC-LTQ-Orbitrap-MS. Four diterpenoids were obtained, including a novel compound: 1α-acetoxy-7α, 14β, 20α-trihydroxy-ent-kaur-16-en-15-one (1); together with three known compounds kamebakaurin (2), lasiokaurin (3), enmenol-1-β-glucoside (4). Their structures were elucidated on the basis of spectroscopic methods in conjunction with published data for their analogues. All compounds were tested for their cytotoxic effects against five human cancer cell lines HCT-116, HepG2, A2780, NCI-H1650 and BGC-823, respectively. Compounds 1 and 2 showed obviously cytotoxic activity against the five cancer cell lines with IC₅₀ ranging from 1.06 to 3.60 μM. Compounds 3 and 4 showed selective cytotoxic activity.     

Cytotoxic and anti-HIV phenanthroindolizidine alkaloids from Cryptocarya chinensis

Bioassay-guided fractionation of the cytotoxic ethanol extract of Cryptocarya chinensis has led to the isolation of 11 compounds, including two phenanthroindolizidine alkaloids [(-)-antofine (1) and dehydroantofine (2)], five pavine alkaloids (3-7), and four proaporphine alkaloids (8-11). The structures of the isolated compounds were determined by means of NMR spectroscopic methods, and supported by HRMS and optical rotation data. Compounds 1 and 2 showed cytotoxic activity against four cancer cell lines, L1210, P388, A549, and HCT-8, with 1 being the most potent against A549 and HCT-8 with EC50 values of 0.002 and 0.001 microg/mL, respectively. In addition, 2 is first reported to exhibit significant anti-HIV activity.     

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.     

Antitumor constituents from the leaves of Carya cathayensis

This study aimed to find cytotoxic chemical constituents from Carya cathayensis leaves (LCC) by using various chromatographic procedures. Identification of the chemical constituents was carried out by various spectroscopic techniques and classical chemical methods. The cytotoxic activity of the constituents was assayed on HeLa and HepG2 cell lines by staining with 3-(4,5-dimethylthiahiazol-2-y1)-2,5-di-phenytetrazolium bromide (MTT). Six flavanoids, namely (1) pinostrobin, (2) pinostrobin chalcone, (3) wogonin, (4) cardamonin, (5) alpinetin and (6) tectochrysin were identified from this species. Compounds 2-6 were isolated from this kind of plant for the first time. MTT results showed that wogonin has a moderate cytotoxic activity with IC(50) values of 17.03?±?2.41 and 44.23?±?3.87?μM against HeLa and HepG2 cell lines, respectively. According to the correlation of primary the structure and activity, 8-methoxy substituent in these flavones may be a major factor of the antitumor activity.     

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.     

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.     

Anticancer effect of three pyrazole derivatives

The evaluation of the cytotoxic properties in vitro of three synthetic tripods containing pyrazole: N,N-bis[(3,5-dimethylpyrazol-1-yl)methyl]aniline (1); N,N-tetrakis[(3,5-dimethylpyrazol-1-yl)methyl]-para-phenylenediamine (2); and N,N-tetrakis-[(1,5-dimethylpyrazol-3-yl)methyl]-para-phenylenediamine (3), was examined for their cytotoxic activity on two tumor cell lines: P815 (murin mastocytoma) and Hep (human laryngeal carcinome). While the compound 2 shows a small cytotoxic activity, compounds 1 and 3 are more cytotoxic against both cell lines. However, this cytotoxicity is more pronounced against Hep cell line (IC50: 3.25 microg mL(-1) for compound 1 and 6.92 microg mL(-1) for compound 3) than P815 cell line (IC50: 17.82 microg mL(-1) for compound 1 and 37.21 microg mL(-1) for compound 3). Statistical analysis shows that the compound 1 is two- to threefold more cytotoxic than compound 3 (P < 0.05). Interestingly, the cytotoxicity induced by compound 1 against Hep cell line is more important than that induced by adriamycin used as a positive control.     

Three new podocarpane-type diterpenoids from callus of Securinega suffruticosa

Three new podocarpane-type diterpenoids, 3beta,12-dihydroxy-13-methyl-6,8,11,13-podocarpatetraen (1), 3beta,12-dihydroxy-13-methyl-5,8,11,13-podocarpatetraen-7-one (2), and 1-(7-hydroxy-2,6-dimethyl-1-naphthyl)-4-methyl-3-pentanone (3) (20(10-->5)-abeo-4,5-seco-5(10),6,8,11,13-podocarpapentaen-3-one) were isolated from callus of Securinega suffruticosa. The structures were elucidated by spectroscopic methods. Compounds 1, 2, and 3 showed cytotoxic activity against five human cancer cell lines (A549, BEL 7402, BGC-823, HCT-8, A2780).