A series of inhibitors of NF-κB based on ursolic acid (UA) derivatives containing functionalized aniline or amide side chains were synthesized and evaluated for inhibition of NF-κB as well as their antitumor effects. These compounds exhibited significant inhibition activity toward NF-κB with IC50 values at micromolar concentrations in the NCI-H460 lung adenocarcinoma cell line. A docking study of the most active compound 5Y8 revealed key interactions between 5Y8 and the active site of NF-κB in which the functionalized amide moiety at the C-28 position and an ester group at the C-3 position were important for improving the activity. In particular, compound 5Y8 appeared to be the most potent compound against the NCI-H460 cell line, and displayed similar efficiency in drug-sensitive versus drug-resistant cancer cell lines, at least partly, by blocking the NF-κB signaling pathway and inducing apoptosis. Mechanistically, compound 5Y8 might trigger the apoptotic signaling pathway. Thus, the rational design of UA derivatives with functionalized aniline or amide side chains offers significant potential for the discovery of a new class of NF-κB inhibitors with the ability to induce apoptosis and reverse multidrug resistance in the NCI-H460 lung adenocarcinoma cell line.

An efficient strategy of using molecularly imprinted solid-phase extraction and high-speed counter-current chromatography (HSCCC) were established for separation and purification of three analogues from Clematis akebioides for the first time. The three analogues, including 26.30 mg caffeic acid, 84.20 mg p-coumaric acid, and 44.40 mg ferulic acid, were obtained from 200.00 mg of the crude sample. The molecularly imprinted polymer was prepared with caffeic acid as template molecule and acrylamide as functional monomers. The results showed that the caffeic acid and its analogues could be well enriched. Then, the extract was purified by HSCCC using a two-phase solvent system consisting of chloroform/acetonitrile/water/acetic acid (10:5:4:0.0004, v/v) and a continuous sample introduction system was adopted. The three organic acids were identified by 1H-NMR and 13C-NMR.

•A novel series of DHAA dipeptide derivatives containing the sulfonamide moiety were synthesized.•Compound 8k exhibited potential inhibitory activity against MMP-3.•Molecular modeling suggested that 8k tightly binds to the active site of MMP-3.•The inhibitors efficiently inhibit the cell migration of human liver cancer cells.•8k induced apoptosis and arrested cell cycle at G1 phase in HepG2 cells.A series of dehydroabietic acid (DHAA) dipeptide derivatives containing the sulfonamide moiety were designed, synthesized and evaluated for inhibition of MMPs as well as the effects of in vitro cell migration. These compounds exhibited relatively good inhibition activity against MMPs with IC50 values in low micromolar range. A docking study of the most active compound 8k revealed key interactions between 8k and MMP-3 in which the sulfonamide moiety and the dipeptide group were important for improving activity. It is noteworthy that further antitumor activity screening revealed that some compounds exhibited better inhibitory activity than the commercial anticancer drug 5-FU. In particular, compound 8k appeared to be the most potent compound against the HepG2 cell line, at least partly, by inhibition of the activity of MMP-3 and apoptosis induction. The treatment of HepG2 cells with compound 8k resulted in inhibition of in vitro cell migration through wound healing assay and G1 phase of cell cycle arrested. In addition, 8k-induced apoptosis was significantly facilitated in HepG2 cells. Thus, we conclude that DHAA dipeptide derivatives containing the sulfonamide moiety may be the potential MMPs inhibitors with the ability to suppress cells migration.Download high-res image (161KB)Download full-size image

A series of antitumor agents based on terminal functionalized dipeptide derivatives containing the thiourea moiety were synthesized and evaluated for antiproliferative activity using a panel of cancer cell lines, and the effects and mechanism of apoptosis induction were determined. These compounds exhibited significant selectivity to different cancer cell lines with IC50 values at micromolar concentrations. In particular, compound I-11 appeared to be the most potent compound, with an IC50 = 4.85 ± 1.44 μM against the NCI-H460 cell line, at least partly, by the induction of apoptosis. Mechanistically, compound I-11 induced the activation of caspase-12 and CHOP, which triggered apoptotic signalling via the ROS-dependent endoplasmic reticulum pathway and arrested the cell cycle at the S phase. Thus, we concluded that dipeptide derivatives containing the thiourea moiety terminally functionalized by electron-withdrawing substituents may be potential antitumor agents for further investigation.

Maleopimaric N-naphthylimides (1–3) underwent slow aR–aS conversion and were induced in a gradual change of different [aR]/[aS] ratio during dissolution in various polar solvents at ambient temperatures. N-Quinoline-imides 2 with 28–100% ee of aR isomer were found to be protonation-controllable under hydrophobic condition. Mechanistic studies showed that this dramatic acid induced change was due to stabilization of the planar transition state by formation of an intramolecular hydrogen bond between the protonated quinoline nitrogen (N+–H) and an imide carbonyl (OC).

Several rhein α-aminophosphonates conjugates (5a–5q) were synthesized and evaluated for in vitro cytotoxicity against HepG-2, CNE, Spca-2, Hela and Hct-116 cell lines. Some compounds showed relatively high cytotoxicity. Especially, compound 5i exhibited the strongest cytotoxicity against Hct-116 cells (IC50 was 5.32 μM). All the synthesized compounds exhibited low cytotoxicity against HUVEC cells. The mechanism of compound 5i was preliminarily investigated by Hoechst 33258 staining, JC-1 mitochondrial membrane potential staining and flow cytometry, which indicated that the compound 5i induced apoptosis in Hct-116 cancer cells. Cell cycle analysis showed that these compound 5i mainly arrested Hct-116 cells in G1 stage. The effects of 5i on the activation of caspases expression indicated that 5i might induce apoptosis via the membrane death receptor pathways. In addition, the binding properties of a model analog 5i to DNA were investigated by methods (UV–vis, fluorescence, CD spectroscopy and FRET-melting) in compare with that of rhein. Results indicated that 5i showed moderate ability to interact ct-DNA.

•Two new terpenoids were isolated from Ligularia przewalskii.•Compound 1 exhibited inhibition against Hep-G2 cells.•Compound 2 showed strong inhibitory activity against MCF-7.•The triterpene skeleton of 1 was firstly found from the genus Ligularia.A phytochemical study of the ethanolic extract of Ligularia przewalskii (Maxim.) Diels led to the isolation of two new terpenoids, (1βH,3βH)-epoxy-olean-13(18)-ene-3α,2-olide (1) and 8β-hydroxy-(10βH)-14β-methyl-6α-angeloyloxy eremophil-7(11)-en-8α,12-olide-15α-oic acid (2), along with 22 known compounds (3–24), of which compounds 3–13 were isolated from this plant for the first time. The structures of these compounds were established on the basis of spectroscopic methods. Compounds 1–2 were evaluated for their in vitro anti-proliferative activities against Hep-G2 and MCF-7 tumour cell lines. Compound 1 exhibited strong inhibitory activity against Hep-G2 cell growth, in contrast to moderate cytotoxic activity against MCF-7 cells. Although compound 2 showed strong inhibitory activity against MCF-7 cell growth, it appeared to have modest activity against Hep-G2 cells.

Series of novel hybrids of alizarin and diamide scaffold (3a–3h, 7a–7h) were designed and synthesized. In vitro antitumor activities of all compounds against HepG-2, CNE, Spca-2, Hct-116, and MGC-803 cell lines were evaluated, and employing standard MTT assay compared with commercial anticancer drug 5-fluorouracil (5-FU). Compounds 7b, 7c, 7d, and 7e showed relatively high cytotoxicity. Especially, compound 7c exhibited the best cytotoxicity against CNE cells with IC50 9.08 µM, which was even stronger than that of 5-FU. All the synthesized compounds exhibited low cytotoxicity against HUVEC cells. The action mechanism of representative compound 7c was preliminarily investigated by flow cytometry, which indicated that the compound can induce cell apoptosis in CNE cells. Cell cycle analysis showed that compound 7c mainly arrested CNE cells in G1 stage. In addition, the binding properties of a model analog 7c to DNA were investigated by different methods (fluorescence, CD spectroscopy), and the results indicated that 7c showed a moderate preference for binding ct-DNA.

A new dicaffeoyl quinic acid, nannoglottisin A, has been isolated from an endemic plant of Nannoglottis ravida, and the structure of the compound was identified by means of spectroscopic analysis.

Phytochemical investigation of the ethanol extract obtained from the aerial parts of the Euphorbia altotibetic PAULS. Grown in China resulted in the isolation of three new cholestane-type and three new ergostane-type steroids (cholest-5-en-2β, 4β-diol; cholest-5-en-1β, 4β-diol; cholest-5-en-1α, 3β, 4α -triol; (22E)-ergosta-7,9,22-trien- 3β-ol β-d-glucoside ; 5α-methoxy-(22E)-ergosta-7,9,22-trien-3β-ol β-d-glucoside ; 6β- methoxy-(22E)-ergosta-7,9,22-trien-3β-ol β-d-glucoside), along with seven known compounds. Their structures were established by extensive one- and two-dimensional NMR spectroscopy, as well as other spectrum and chemical analysis. The isolated new steroids exhibited potent anti-tumor activity against the HeLa cell and Hep-G2 cell with the 50% inhibiting concentration values ranging from 1.9 to 9.2 μg/mL.Graphical abstractPhytochemical investigation of the ethanol extract obtained from the aerial parts of the Euphorbia altotibetic PAULS. grown in China resulted in the isolation of three new cholestane and three new ergostane-type steroids. The isolated new steroids exhibited potent anti-tumor activity against the Hela cell and Hep-6 cell.Download full-size imageHighlights► Three new cholestane and three new ergostane-type steroids were isolated. ► The new steroids exhibited potent cytotoxic activity against HeLa and Hep-6 cell. ► It is the first report of in vitro cytotoxicity of steroids from Euphorbia altotibetic. ► The research deepens the understanding of chemical composition of Euphorbia plant.