A New Ester Isolated from Ferula assa-foetida L.

A new caffeic acid cinnamyl ester (1) was isolated from the n-hexane-soluble fraction of an MeOH extract of the gum resin of Ferula assa-foetida L. The structure was determined to be (2E)-3,4-dimethoxycinnamyl-3-(3,4 diacetoxyphenyl) acrylate on the basis of spectroscopic data including 1D- and 2D-NMR. Compound 1 showed moderate activity for inhibiting LPS-induced nitric oxide production in murine macrophage RAW264.7 cells, with an IC₅₀ value of 54.9 μm.     

In vitro cytotoxic activity of extracts and isolated constituents of Salvia leriifolia Benth. against a panel of human cancer cell lines

In the course of recent efforts to identify new potential antiproliferative active principles, Salvia leriifolia extracts and isolated constituents were evaluated for their cytotoxic activity against a panel of human cancer cell lines, including renal adenocarcinoma (ACHN), amelanotic melanoma (C32), colorectal adenocarcinoma (Caco‐2), lung large cell carcinoma (COR‐L23), malignant melanoma (A375), lung carcinoma (A549), and hepatocellular carcinoma (Huh‐7D12) cells. The hexane and CH₂Cl₂ extracts showed the strongest cytotoxic activity against the C32 cell line with IC₅₀ values of 11.2 and 13.6 μg/ml, respectively, and the AcOEt extract was the most active extract against the COR‐L23 cell line (IC₅₀ of 20.9 μg/ml). Buchariol, a sesquiterpene obtained by biofractionation of the CH₂Cl₂ extract, exhibited a higher activity than the positive control vinblastine against the C32 and A549 cell lines (IC₅₀ values of 2.1 and 12.6 μM , resp.). Interesting results were also obtained for naringenin, a flavonoid isolated from the AcOEt extract, which exhibited a strong cytotoxic activity against the C32, LNCaP, and COR‐L23 cell lines (IC₅₀ values of 2.2, 7.7, and 33.4 μM , resp.), compared to vinblastine (IC₅₀ values of 3.3, 32.2, 50.0 μM , resp.). None of the tested compounds affected the proliferation of skin fibroblasts (142BR), suggesting a selective activity against tumor cells.     

Chemical constituents of Mallotus macrostachyus growing in Vietnam and cytotoxic activity of some cycloartane derivatives

Two new cycloartane derivatives, macrostachyosides A (1) and B (2), and seventeen known compounds were isolated from the methanol extract of Mallotus macrostachyus leaves. Their structures were elucidated by NMR and MS data. Macrostachyosides A (1) and B (2) showed significant cytotoxic activities on KB (epidermoid carcinoma) and LU-1 (lung adenocarcinoma) human cancer cell lines with IC₅₀ values ranging from 4.31 ± 0.09 to 7.12 ± 0.07 μg/mL.     

Casearin X,Its Degradation Product and Other Clerodane Diterpenes from Leaves of Casearia sylvestris: Evaluation of Cytotoxicity against Normal and Tumor Human Cells

An EtOH extract of the leaves of Casearia sylvestris afforded new clerodane diterpene, casearin X, together with the known compounds casearins B, D, L, and O, and caseargrewiin F. Casearin X degraded to the corresponding dialdehyde when stored in CDCl₃. The diterpenes isolated were cytotoxic to human cancer cell lines, with caseargrewiin F being the most active and the new clerodane, casearin X, the second active compound with IC₅₀ values comparable to the positive control doxorubicin. All isolated diterpenes showed lower activities against normal human cells than against cancer cell lines, which might indicate a possible selective action on cancer cells. Casearin X dialdehyde was not cytotoxic to cancer cells indicating that the occurrence of these CO groups at C(18) and C(19) is incompatible with the cytotoxic activity.     

Antioxidant activity of the chemical constituents from the flower buds of <Emphasis Type="Italic">Magnolia denudata</Emphasis>

The scavenging activity of the flower buds of Magnolia denudata Desrousseaux on reactive oxygen species (ROS) was evaluated using 2′,7′-dichlorofluorescin diacetate (DCFH-DA) in HT 1080 cells. Methanol (MeOH) and dichloromethane (CH₂Cl₂) extracts inhibited dose-dependently generation of ROS in the cellular system. MeOH and CH₂Cl₂ extracts were combined and fractionated with n-hexane, 85% aqueous MeOH, and n-butanol (n-BuOH). Both n-hexane-soluble and 85% aqueous-soluble fractions showing strong radical-scavenging activity in the cellular system were further separated by diverse chromatographic methods to give five known lignans (1–5). All these compounds exhibited significant radical-scavenging effect on intracellular ROS in a dose-dependent manner. Their scavenging activity on various reactive oxygen species (ROS) was also evaluated using electron spin resonance (ESR) spin-trap techniques.     

Fatty acid synthase inhibitors from the hulls of Nephelium lappaceum L

Natural products inhibiting fatty acid synthase (FAS) are appearing as potential therapeutic agents to treat cancer and obesity. The bioassay-guided chemical investigation of the hulls of Nephelium lappaceum L. resulted in the isolation of ten compounds (1–10) mainly including flavonoids and oleane-type triterpene oligoglycosides, in which all of the compounds were isolated from this plant for the first time. Additionally, compounds 8 and 9 were new hederagenin derivatives and were elucidated as hederagenin 3-O-(2,3-di-O-acetyl-α-l-arabinofuranosyl)-(1→3)-[α-l-rhamnopyranosyl(1→2)]-β-l-arabinopyranoside and hederagenin 3-O-(3-O-acetyl-α-l-arabinofuranosyl)-(1→3)-[α-l-rhamnopyranosyl-(1→2)]-β-l-arabinopyranoside, respectively. All these isolates were evaluated for inhibitory activities of FAS, which showed these isolates had inhibitory activity against FAS with IC₅₀ values ranging from 6.69 to 204.40 μM, comparable to the known FAS inhibitor EGCG (IC₅₀ = 51.97 μM). The study indicates that the hulls of Nephelium lappaceum L. could be considered as potential sources of promising FAS inhibitors and the oleane-type triterpene oligoglycosides could be considered as another type of natural FAS inhibitors.     

Anti-angiogenic,apoptotic and matrix metalloproteinase inhibitory activity of Withania somnifera (ashwagandha) on lung adenocarcinoma cells

IntroductionWithania somnifera belongs to the family Solanaceae, known as Queen of medicinal plants for its enormous use in the medicinal field. Traditionally ashwagandha is used to treat several neurological disorders. This study evaluates the cytotoxic, apoptotic, antiangiogenic and matrix metalloproteinase (MMP) inhibitory activity of W. somnifera on lung adenocarcinoma.MethodologyAqueous and ethanolic extracts were prepared from the roots of the W. somnifera. Qualitative and quantitative phytochemical analyses were performed using the standard protocols. Cytotoxicity was assessed using MTT assay. Further experiments were carried out with IC₅₀ concentration of the extract. Apoptosis and DNA damage were evaluated using AO-EB dual staining, Hoechst staining and Comet assay. Effect of the extract on cell migration was evaluated using scratch assay. Angiogenesis inhibition was evaluated using in ovo CAM assay and angiogenic pathway alterations were evaluated using qRT-PCR and western blotting. Autophagy induction was studied via western blotting.ResultsIn this study, we found antioxidant activity and the presence of certain secondary metabolites in the ethanolic extracts. The extract showed cytotoxic activity on lung adenocarcinoma cells with an IC₅₀ of 99.7 μg/ml. The extract showed significant anti-angiogenic, apoptotic and autophagy induction activity. W. somnifera extract induced significant decrease in the cell migration at lower concentrations indicating the anti-migratory potential.ConclusionOur investigation revealed ethanolic extract of W. somnifera possess significant anti-angiogenic and MMP inhibitory activity and helps in inhibiting the lung adenocarcinoma cells proliferation. Further, our study revealed that the enhanced autophagy induction and apoptotic effects of W. somnifera are responsible for the potential anticancer activity of the extract.     

The extract of leaves of Acer truncatum Bunge: A natural inhibitor of fatty acid synthase with antitumor activity

Fatty acid synthase (FAS) has been identified as a potential antitumor target. The extract from the leaves of Acer truncatum Bunge (Extr) was prepared to assay its inhibitory activity against FAS, which was isolated from duck liver, and the correlated antitumor bioactivity. Its inhibition of FAS is composed of reversible fast-binding inhibition, IC₅₀ = 0.7 μg/ml, and irreversible slow-binding inhibition following saturation kinetics with a dissociation constant of 0.68 μg/ml and a limiting rate constant of 0.0288 min^{? 1}. The Extr exhibited different type of inhibitions against the three substrates in the FAS overall reaction. Compared with EGCG in inhibition constant and IC₅₀ value, the Extr appeared to be a more efficient inhibitor, and exhibited a considerable inhibition against the growth of four kinds of cancer cells (patent application number 200510068054.2). It was infered that the inhibitory activity is likely attributable to the co-operative effect of the components.     

New Steroidal Glycosides from Rhizomes of Clintonia udensis

A total of 10 steroidal glycosides, together with three new spirostanol glycosides (6–8), a new furostanol glycoside (9), and a new cholestane glycoside (10), were isolated from the rhizomes of Clintonia udensis (Liliaceae). The structures of the new compounds were determined on the basis of extensive spectroscopic analyses, including 2-D nuclear magnetic resonance (NMR) data, and of hydrolytic cleavage followed by chromatographic or spectroscopic analyses. The isolated glycosides were evaluated for their cytotoxic activity against HL-60 leukemia cells. Spirostanol glycosides 1 and 2, and furostanol glycoside 4 showed cytotoxic activity with IC₅₀ values of 3.2±0.02, 2.2±0.12, and 2.2±0.06 μg/ml, respectively. Neither the spirostanol and furostanol saponins with a hydroxy group at C-1 (6 and 9) and C-12 (7 and 8) nor cholestane glycosides (5 and 10) exhibited apparent cytotoxic activity at a sample concentration of 10 μg/ml.     

Amperometric Detection of Reduced Nicotinamide Adenine Dinucleotide Using a Film-covered Organic Salt Electrode

A new N-acylated serinol, inconspicamide (1), was isolated from the marine sponge, Stelletta inconspicua, together with a glyceryl ether (2). Their structures were determined on the basis of spectroscopic data and the modified Mosher analysis. They exhibited moderate cytotoxic activity against HeLa human cervical cancer cells.     

Synthesis,antitumor screening and cell cycle analysis of novel benzothieno[3,2-b]pyran derivatives

Abstract

Three series of benzothiophene derivatives were designed and synthesized as cytotoxic agents. The compounds were subjected to in vitro antitumor screening at the National Cancer Institute (NCI), Bethesda, MD. The results of the single dose screening indicated that only the benzothieno[3,2-b]pyran series 3a–f exhibited potent and broad spectrum cytotoxic activity and was subjected to five dose cytotoxic screening. The most active compound in this study was 2-amino-6-bromo-4-(4-nitrophenyl)-4H-[1]benzothieno[3,2-b]pyran-3-carbonitrile (3e) with MG-MID GI₅₀, TGI, and LC₅₀ values of 0.11, 7.94 and 42.66?μM, respectively. Compound 3e exhibited broad spectrum anticancer activity against a panel of 59 cell lines. To elucidate the underlying mechanism of compound 3e cytotoxic activity, we examined its effect on cell cycle progression and its ability to induce apoptosis using human colon adenocarcinoma cell line (HCT-116). The effect of compound 3e on the cell cycle progression indicated that exposure of HCT-116 cells to compound 3e for 24 and 48?h, induced a significant disruption in the cell cycle profile including time dependent decrease in cell population at G1 phase with concomitant increase in pre-G and G2/M cell population. Moreover, compound 3e induced time dependent increase in the percentage of early and late apoptotic and necrotic cell population. In conclusion, we were able to successfully design a new series of benzothieno[3,2-b]pyran derivatives with potent cytotoxic activity and their mechanism of cytotoxicity was examined.     

Evaluation of the inhibitory activities of aceraceous plants on fatty acid synthase

Fatty acid synthase (FAS) is a very significant lipogenic enzyme participating in energy metabolism in vivo and has been reported as a potential new therapeutic target for cancer treatment. The extracts from sixteen Aceraceae were prepared to assay their inhibitory activities against duck liver FAS and their correlated antitumor bioactivity. Their inhibition of FAS was composed of a reversible fast-binding inhibition, by which 0.41 μg/mL of the A. campestre extract inhibits 50% FAS activity, and an irreversible slow-binding inhibition with inactivation rate constants, k_obs, ranging between 1.5 × 10^{? 3} and 10.6 × 10^{? 3} min^{? 1}. Three Aceraceae extracts were selected from their smaller IC₅₀ values to study different type of inhibitions against the three substrates in the FAS overall reaction. As compared with other reported FAS inhibitors including EGCG with regard to inhibition constant and IC₅₀ value, the extracts appeared to be more efficient inhibitors, and exhibited a considerable inhibition against the growth of five types of cancer cells (China patent application number 200610088901.6), which may be related to the inhibition of lipogenesis in these cells.     

A Lichen Substance as an Antiproliferative Compound against HL-60 Human Leukemia Cells: 16-O-Acetyl-leucotylic Acid Isolated from Myelochroa aurulenta

The lichen substance, 16-O-acetyl-leucotylic acid (1), was isolated from an acetone extract of Myelochroa aurulenta and found to exhibit antiproliferative activity against HL-60 human leukemia cells. This is the first report on its anti-leukemia activity (EC₅₀=21 μM) which is greater than that of leucotylic acid (2) and the structurally related anti-tumor agent, betulinic acid (4).     

Cytotoxic activity of hirsutanone,a diarylheptanoid isolated from Alnus glutinosa leaves

BackgroundThe low efficacy of cancer therapy for the treatment of patients with advanced disease makes the development of new anticancer agents necessary. Because natural products are a significant source of anticancer drugs, it is important to explore cytotoxic activity of novel compounds from natural origin.PurposeThe aim of this work is to evaluate the cytotoxic capacity of hirsutanone, a diarylheptanoid isolated from Alnus glutinosa leaves. Hirsutanone cytotoxic way of action was also studied.Material and methodsThe cytotoxic ability of Alnus glutinosa leaves ethyl acetate extract was studied over HeLa and PC-3 cell lines, with the MTT colorimetric assay. Hirsutanone was isolated from this extract using chromatographic methods, and its structure elucidated by spectroscopic analysis. HT-29 cell viability after hirsutanone treatment was determined using SRB assay. In order to understand hirsutanone way of action, cytotoxicity was evaluated adding the diarylheptanoid and antioxidants. DNA topoisomerase II (topo II) poison activity, was also evaluated using purified topo II and a supercoiled form of DNA that bears specific topo II recognition and binding region; topo II poisons stabilize normally transient DNA-topo II cleavage complexes, and lead an increased yield of linear form as a consequence of a lack of double-strand breaks rejoining.ResultsThe diarylheptanoid hirsutanone was isolated from Alnus glutinosa (L.) Gaertn. (Betulaceae) leaves extract that showed cytotoxic activity against PC-3 and HeLa cell lines. Hirsutanone showed cytotoxic activity against HT-29 human colon carcinoma cells. Pre-treatment with the antioxidants NAC (N-acetylcysteine) and MnTMPyP (Mn(III)tetrakis-(1-methyl-4-pyridyl)porthyrin) reduced this activity, suggesting that reactive oxygen species (ROS) participate in hirsutanone-induced cancer cell death. Using human topo II and a DNA supercoiled form, hirsutanone was found to stabilize topo II-DNA cleavage complexes, acting as a topo II poison.ConclusionOur data suggest that, like curcumin, an induction of oxidative stress and topo II-mediated DNA damage may play a role in hirsutanone-induced cancer cell death. Since both compounds share similar structure and cytotoxic profile, and curcumin is in clinical trials for the treatment of cancer, our results warrant further studies to evaluate the anticancer potential of hirsutanone.     

Erymildbraedin A and B,two novel cytotoxic dimethylpyrano-isoflavones from the stem bark of Erythrina mildbraedii: evaluation of their activity toward endocrine cancer cells

Two new dimethylpyrano-isoflavones, named erymildbraedin A (4) and B (5), were isolated from the stem bark of the Cameroonian medicinal plant Erythrina mildbraedii, along with four known ones, the linear congeners, scandenone (1), erysenegalinsein M (2), 5,4′-dihydroxy-2′-methoxy-8-(3,3-dimethylallyl)-2″,2″-dimethylpyrano[5,6:6,7]isoflavone (3), and the angular isoflavone eryvarin B (6), and two other compounds, fraxidin and scoparone. Their structures were elucidated by the usual spectroscopic methods and isoflavone effects on the growth of human breast, prostate, and endometrial adenocarcinoma cells were determined. Isoflavones 1, 3, and 6 strongly inhibited the growth of all three cell lines, supporting the notion that a non-oxidized isoprenyl group at C-8 is requisite for cytotoxic activity.     

Novel cytotoxic chalcones from Litsea rubescens and Litsea pedunculata

Two novel flavonoids with chalcone skeleton, together with seven known flavonoids, were isolated from the stem barks of Litsea rubescens and Litsea pedunculata. The structures of the new compounds were elucidated on the basis of spectral methods including IR, UV, 1D and 2D NMR. The new chalcones were found to contain the rare epoxy or ethylidenedioxy group. This is the first report on the presence of chalcone in the plant genus Litsea. The cytotoxic potential of two new chalcones was evaluated in vitro against three human tumor cell lines. Both new chalcones displayed potent cytotoxic activities against myeloid leukaemia (HL-60) and epidermoid carcinoma (A431) cell lines and more active than cisplatin (DDP). Interestingly, compound 1 exhibited cytotoxic activity against HL-60 with IC₅₀ value 2.1-fold more sensitive to DDP.     

Cytotoxic and antioxidant triterpene saponins from Butyrospermum parkii (Sapotaceae)

Three new triterpenoid saponins, elucidated as 3-O-β-d-glucopyranosyloleanolic acid 28-O-β-d-xylopyranosyl-(1→4)-α-l-rhamnopyranosyl-(1→2)-β-d-xylopyranoside (parkioside A, 1), 3-O-[β-d-apifuranosyl-(1→3)-β-d-glucopyranosyl]oleanolic acid 28-O-[β-d-apifuranosyl-(1→3)-β-d-xylopyranosyl-(1→4)-[α-l-rhamnopyranosyl-(1→3)]-α-l-rhamnopyranosyl-(1→2)β-d-xylopyranoside (parkioside B, 2) and 3-O-β-d-glucuronopyranosyl-16α-hydroxyprotobassic acid 28-O-α-l-rhamnopyranosyl-(1→3)-β-d-xylopyranosyl-(1→4)-α-l-rhamnopyranosyl-(1→2)-β-d-xylopyranoside (parkioside C, 3), were isolated from the n-BuOH extract of the root bark of Butyrospermum parkii, along with the known 3-O-β-d-glucopyranosyloleanolic acid (androseptoside A). The structures of the isolated compounds were established on the basis of chemical and spectroscopic methods, mainly 1D and 2D NMR data and mass spectrometry. The new compounds were tested for both radical scavenging and cytotoxic activities. Compound 2 showed cytotoxic activity against A375 and T98G cell lines, with IC₅₀ values of 2.74 and 2.93 μM, respectively. Furthermore, it showed an antioxidant activity comparable to that of Trolox or butylated hydroxytoluene (BHT), used as controls, against 2,2-diphenyl-1-picryl hydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), oxygen and nitric oxide radicals.     

Five new triterpenoid saponins from the Roots of Camellia oleifera C. Abel with cytotoxic activities

Five new triterpenoid saponins, oleiferosides P–T (1–5) were isolated from the EtOH extract of the roots of Camellia oleifera C. Abel. The structures of saponins 1–5 were elucidated on the basis of integrated spectroscopic techniques. All the compounds were characterized to be oleanane-type saponins with sugar moieties linked to the C-3 of the aglycone. By using the MTT assay, an in vitro analysis of the cytotoxic activities of these saponins on the human tumor cell lines (lung adenocarcinoma A549 cells, hepatic carcinoma SMMC-7721 cells and breast cancer MCF-7 cells). Among them, compound 4 showed a certain cytotoxic activity against all the tested cell lines.     

Synthesis and cytotoxic activities of novel copper and silver complexes of 1,3-diaryltriazene-substituted sulfonamides

In this study, a series of 10 novel copper (II) and silver complexes of 1,3-diaryltriazene-substituted sulfonamides was synthesised. All the synthesised ligands and their metal complexes were assessed for in vitro cytotoxicity against human colorectal adenocarcinoma (DLD-1), cervix carcinoma (HeLa), breast adenocarcinoma (MDA-MB-231), colon adenocarcinoma (HT-29), endometrial adenocarcinoma (ECC-1), prostate cancer (DU-145 and PC-3), normal embryonic kidney (HEK-293), normal prostate epithelium (PNT-1A), and normal retinal pigment epithelium (ARPE-19) cells. Most of the metal complexes from the series showed to be more active against all cancerous cells than the uncomplexed 1,3-diaryltriazene-substituted sulfonamides, and lower cytotoxic effects observed on normal cells. Most of the Cu (II) and Ag (I) metal complexes from the presented series showed high cytotoxic activity against HeLa cells with IC₅₀ values ranging from 2.08 to >300?µM. Specifically, compound L₃-Ag showed one of the highest cytotoxicity against all cancer cell lines with IC₅₀ values between 3.30 to 16.18?µM among other tested compounds.     

The chemical constituents of Piper kadsura and their cytotoxic and anti-neuroinflammtaory activities

The n-hexane and CHCl₃ soluble fractions of the MeOH extract of the aerial parts of Piper kadsura were found to potently inhibit nitric oxide (NO) production in LPS-activated BV-2 cells, a microglial cell line. From the active fractions, a new stereoisomer of guaiane sesquiterpene, 1α,5β-guai-4(15)-ene-6β,10β-diol, kadsuguain A (1) and a new cyclohexadienone, kadsuketanone A (2), together with twelve known compounds (3–14) were isolated. The structures of these compounds were elucidated by extensive NMR spectral studies. The absolute configuration of 2 was determined by circular dichroism (CD) spectra. Compounds 2, 6, and 11–14 significantly inhibited both nitric oxide (NO) and prostaglandin E₂ (PGE₂) production in the LPS-activated microglia cells. In addition, compounds 4, 6, and 11–14 exhibited cytotoxicity against the A549, SK-OV-3, SK-MEL-2, and HCT15 human tumour cells.