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Nitidumpeptins A and B (1 and 2), two novel cyclic hexapeptides, were isolated from the herb Zanthoxylum nitidum var. tomentosum. Their planar structures were elucidated based on NMR and MS spectrometric analysis, and the absolute configurations were determined by the Marfey's method. Structurally, 1 is a unique peptide with a backbone bearing a pyrrolidine-2,5-dione unit, which is the first occurrence moiety specifically in a naturally occurring cyclohexapeptide. The total synthesis of 1 and 2 was achieved by solution-phase in parallel with solid-phase peptide synthesis, and their absolute configurations were further confirmed. The combination of 2 with gefitinib exhibited synergistic antiproliferative activity in acquired gefitinib-resistant non-small cell lung cancer cells (HCC827-gef). The underlying mechanism for the antiproliferative activity of 2 was in part associated with the suppression of YAP expression in HCC827-gef cells.

Series of novel alizarin and phosphoryl amino acid scaffold (4a–4d, 8a–8d) were synthesized and evaluated for the suppression of cancer cell proliferation in vitro against MGC-803, HepG2, T24, NCI-H460, and SK-OV-3 cell lines by standard 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay compared with commercial anticancer drug doxorubicin. Interestingly, all newly synthesized compounds exhibited relatively high cytotoxicity compared with alizarin and low cytotoxicity against human normal liver cell line HL-7702 cells. Especially, compound 8d showed the best cytotoxicity against SK-OV-3 cells with IC50 7.09 µM, which was slightly worse than that of drug doxorubicin. The cell apoptosis-inducing activity of representative compound 8d in SK-OV-3 cells revealed that the anticancer activity of this compound depended on apoptosis of cancer cells via regulation of Bcl-2 family members, activation of caspase-9 and caspase-3. Cell cycle analysis confirmed that compound 8d mainly arrested SK-OV-3 cells in G2 stage. In addition, molecular docking studies were performed to position compound 8d into the telomerase (5CQG) active site to determine the probable binding model.

Several N-aryl maleopimaric acid diimides (3a-3d, 4a-4g) were synthesized and evaluated their topoisomerase I inhibitory activities along with cytotoxicities against NCI, MGC-803, Bel-7404 and Hct-116 cell lines. The pharmacological dates revealed that most of structure analogs exhibited moderate to high levels of anticancer activities against the tested cancer cell lines. Compound 4g with phenylalanine substituent exhibited significant cytotoxicity against MGC-803 and Hct-116 cells (IC 50 was 9.85±1.24 and 8.47±0.95 µM, respectively). All the synthesized compounds exhibited no cytotoxicity against HUVEC cells. In addition, maleopimaric diimides showed stronger cytotoxicity and topoisomerase I inhibitory activity compared to that of maleopimaric acid. Structure–activity relationship study showed that carboxyl and diimide moieties were important to display Topo I inhibitory activities. Further experiments proved that 4g could induce apoptosis of MGC-803 cells. In addition, the further mechanisms of compound 4g-induced apoptosis in MGC-803 cells demonstrated that compound 4g induced the activations of caspase-4, caspase-8 and caspase-3 for causing cell apoptosis, and altered antiand pro-apoptotic proteins. Moreover, cell cycle analysis indicated that the derivative 4g mainly arrested MGC-803 cells in S stage.

A series of novel asiatic acid (AA) derivatives containing α-aminophosphonate were designed and synthesized as antitumor agents. In vitro antitumor activities of these compounds against five cancer cell lines (A549, Hct-116, T24, Spca-2 and SK-OV-3 cell) and a normal cell line (HUVEC cell) were evaluated, employing standard MTT assay. Antitumor activities screening result indicated that many target compounds displayed moderate to high levels of antitumor activities compared with AA, 5-fluorouracil (5-FU) and cisplatin, and exhibited much lower cytotoxicity against normal cell than 5-FU and cisplatin. In addition, the mechanism of representative compound 3d was preliminarily investigated by AO/EB staining, Hoechst 33258 staining, JC-1 mitochondrial membrane potential staining, flow cytometry and western blot. Compound 3d inducing apoptosis involved intracellular Ca2+ production, the loss of mitochondrial membrane potential and intracellular reactive oxygen species (ROS) production. Western blot analysis also demonstrated that compound 3d treatment triggered the mitochondrial apoptotic pathway, indicating by changing Bax/Bcl-2 ratios, cytochrome c release, and caspase-9 activation. Moreover, the cell cycle analysis showed that compound 3d may confine T24 cells in G1/S phase mainly through the p53-dependent pathway. Together, these results implied a critical role of ROS, caspase-9 and p53 in compound 3d-inducing G1/S arrest and apoptosis of T24 cells.

Site-specific conjugation of small molecules to antibody molecules is a promising strategy for generation of antibody-drug conjugates. In this report, we describe the successful synthesis of a novel bifunctional molecule, 6-(azidomethyl)-2-pyridinecarboxyaldehyde (6-AM-2-PCA), which was used for conjugation of small molecules to peptides and antibodies. We demonstrated that 6-AM-2-PCA selectively reacted with N-terminal amino groups of peptides and antibodies. In addition, the azide group of 6-AM-2-PCA enabled copper-free click chemistry coupling with dibenzocyclooctyne-containing reagents. Bifunctional 6-AM-2-PCA mediated site-specific conjugation without requiring genetic engineering of peptides or antibodies. A key advantage of 6-AM-2-PCA as a conjugation reagent is its ability to modify proteins in a single step under physiological conditions that are sufficiently moderate to retain protein function. Therefore, this new click chemistry-based method could be a useful complement to other conjugation methods.

A series of novel coumarin-containing α-aminophosphonates were synthesized and evaluated for their antitumor activities against Human colorectal (HCT-116), human nasopharyngeal carcinoma (human KB) and human lung adenocarcinoma (MGC-803) cell lines in vitro. Compared with 7-hydroxy-4-methylcoumarin (4-MU), most of the derivatives showed an improved antitumor activity. Compound 8j (diethyl 1-(3-(4-methyl-2-oxo-2H-chromen-7-yloxy) propanamido)-1-phenylethyl-Phosphonate), with IC50 value of 8.68 μM against HCT-116 cell lines, was about 12 fold than that of unsubstituted parent compound. The mechanism investigation proved that 8c, 8d, 8f and 8j were achieved through the induction of cell apoptosis by G1 cell-cycle arrest. In addition, the further mechanisms of compound 8j-induced apoptosis in HCT-116 cells demonstrated that compound 8j induced the activations of caspase-9 and caspase-3 for causing cell apoptosis, and altered anti- and pro-apoptotic proteins. DNA-binding experiments suggested that some derivatives bind to DNA through intercalation. The results seem to imply the presence of an important synergistic effect between coumarin and aminophosphonate, which could contribute to the strong chelating properties of aminophosphonate moiety.

A series of novel ursolic acid (UA) derivatives modified at the C-3 and the C-28 positions were designed and synthesized in an attempt to develop potential antitumor agents. The in vitro cytotoxicity were evaluated against five cancer cell lines (MGC-803, HCT-116, T24, HepG2 and A549 cell lines) and a normal cell (HL-7702) by MTT assay. The screening results indicated that some of these target compounds displayed moderate to high levels of antiproliferative activities compared with ursolic acid and 5-fluorouracil (5-FU), and exhibited much lower cytotoxicity than 5-FU, indicating that the targeted compounds had selective and significant effect on the cell lines. The induction of apoptosis and affects on the cell cycle distribution of compound 6r were investigated by acridine orange/ethidium bromide staining, Hoechst 33258 staining, JC-1 mitochondrial membrane potential staining and flow cytometry, which revealed that the antitumor activity of 6r was possibly achieved through the induction of cell apoptosis by G1 cell-cycle arrest. Western blot and qRT-PCR (quantitative real-time PCR) experiments demonstrated that compound 6r may induce apoptosis through both of intrinsic and extrinsic apoptosis pathway.

In an effort to develop potent anti-cancer chemopreventive agents, a novel series of bisindole derivatives bearing oxime moiety were synthesized. Structures of all compounds were characterized by NMR and HRMS. Anti-proliferative activities for all of these compounds were investigated by the method of MTT assay on 7 human cancer lines and the normal cell lines (HUVEC). Most of them showed a noteworthy anti-cancer activity in vitro, the half maximal inhibitory concentration (IC50) value is 4.31 μM of 4e against T24. The results from Hoechst 33258 and acridine orange/propidium iodide staining as well as annexinV-FITC assays provided evidence for an apoptotic cell death. The further mechanisms of compound 4e-induced apoptosis in T24 cells demonstrated that compound 4e induced the productions of ROS, and altered anti- and pro-apoptotic proteins, leading to mitochondrial dysfunction and activations of caspase-9 and caspase-3 for causing cell apoptosis. Moreover, the cell cycle analysis and western-blot analysis indicated that compound 4e effectively arrested T24 cells in G1 stage and possibly has an effect on cell cycle regulatory proteins particularly cyclin D1.

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.

Eleven new 2-O-side-chain derivatives of alizarin were synthesized via esterification, substitution, hydrolysis, or elimination reactions. The structures of all the products were confirmed by 1H NMR, MS, and elemental analysis. Compared with alizarin, most of the derivatives had significantly higher DNA binding affinity based on interaction with ct-DNA. In particular, compound 8 exhibited the best cytotoxicity against HeLa cells with IC50 20 μM and could induce HeLa cells apoptosis.

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.

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).

A series of novel coumarin-containing α-aminophosphonates with two chiral centers were synthesized and a single-crystal structure of compound 8g (8g′, (R)-diethyl ((S)-2-(4-methyl-2-oxo-2H-chromen-7-yloxy)propanamido)(2-bromophenyl)methylphosphonate) was obtained. The in vitro antitumor activities of compound 8a–8g′ against human pulmonary carcinoma cell line (A549), human nasopharyngeal carcinoma (human KB), and human lung adenocarcinoma (MGC-803) cell lines were evaluated. Some compounds showed relatively high cytotoxicity. Compared with 8g, 8g′ exhibited an improved activity against three tumor cells, which was evidenced by the IC50 that was four- to five-fold lower than those for 8g. The influence of chirality was also observed in DNA-binding assay of 8g and 8g′. 8g′ exhibited higher binding constant (1.96 × 103 M−1) as compared to 8g (1.69 × 103 M−1).

Maleopimaric acid N-aryl imides (2) and methyl maleopimaric acid N-aryl imides (3) were designed and synthesized. Their atropisomers (A and B) were separated into their enantiomeric pure forms and the anti-proliferative activity was tested against NCI, A549, Hep G-2, MGC-803 and Hct-116 cell lines, respectively. A significant difference in the level of cytotoxicity was observed between R and S conformers. Atropisomers A with an R configuration exhibited significant toxicity (the IC50 values ranging from 7.51 to 32.1 μM). Further experiments proved that antitumor activity of 2A was achieved through the induction of cell apoptosis by G1 cell-cycle arrest.

A series of novel thiourea α-aminophosphonate derivatives containing DHA structure was designed and synthesized as antitumor agents. Their inhibitory activities against the NCI-H460 (lung), A549 (lung adenocarcinoma), HepG2 (liver) and SKOV3 (ovarian) human cancer cell lines were estimated using MTT assay in vitro. The screening results revealed that many compounds exhibited moderate to high levels of antitumor activities against the tested cancer cell lines and that most demonstrated more potent inhibitory activities compared with the commercial anticancer drug 5-fluorouracil. The mechanism of compound 5f was preliminarily investigated by acridine orange/ethidium bromide staining, Hoechst 33258 staining, JC-1 mitochondrial membrane potential staining, TUNEL assay, DNA ladder assay and flow cytometry, which indicated that the compound can induce cell apoptosis in A549 cells.

Chiral alcohols(3, 5) were synthesized in optically pure forms from easily available rosin acid in short-steps. A comprehensive protocol for the enantiomeric excess assays of mono-or di-functional-grouped chiral secondary amine or alcohol has been established with them used as chiral auxiliary for chiral phosphorus derivatizing agents(CPDAs) in 31P NMR tests. Chemical shift difference(Δδ P) values ranging from 4.5 to 0.15 between two diastereoisomers of the CPDAs and the aryl substrates were obtained. Positive Δδ R-S was observed for all the tested alcohol P(III) and P(V) derivatives, while negative Δδ R-S was observed for all the amines.

A series of inhibitors of 20S proteasome based on terminal functionalized dipeptide derivatives containing the thiourea moiety were synthesized and evaluated for inhibition of 20S proteasome and the effects of multidrug-resistance reversers. These compounds exhibited significant selectivity to the β5-subunit of the human 20S proteasome with IC50 values at submicromolar concentrations. A docking study of the most active compound 6i revealed key interactions between 6i and the active site of the 20S proteasome in which the thiourea moiety and a nitro group were important for improving activity. In particular, compound 6i 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 inhibition of the activity of 20S proteasome and induce apoptosis. In addition, 6i-induced apoptosis was significantly facilitated in NCI-H460/DOX cells that had been pretreated with inhibitors of P-gp. Mechanistically, compound 6i might trigger apoptotic signalling pathway. Thus, we conclude that dipeptide derivatives containing the thiourea moiety may be the potential inhibitors of proteasome with the ability to reverse multidrug resistance.

Dali boasts brilliant local culture and ethnic folk customs.Dali culture is a fusion of cultures such as the central plain, Tibetan culture, southeast Asia culture and the local ethnic culture ; is also a long history of brilliant ancient culture in China's southwestern minority region;and is an important part of Chinese culture.This article through analysis of space layout of Dali Bai local-style dwelling houses building to idendity the rationality and possibility of combining it with local new rural construction.

Compared with the column style of Chinese traditional and Western classical from chapiter, trunk, column base in detail. Analysis of the column of the Eastern and Western Art Deco and shape differences. By comparing ,absorb the essence of both for the theoretical and practical of modern style column type decoration.

Chemical investigations of the whole plant ethanol extract of Rubus phoenicolasius led to the isolation and identification of a new pregnane glycoside, 3-O-β-glucopyranosyl-3β,15β-dihydroxypregn-5-en-20-one (1), along with other nine known compounds (2-10). All the isolates were reported from this plant for the first time. The structure of compound 1 was determined by detailed analysis of its spectral data including 1D and 2D NMR. In vitro anti-proliferative activities of compounds 1-3 on MCF-7 and NCI-H460 tumour cell lines were evaluated, and compound 1 was active against the two cell lines with IC50 values of 15.6 and 13.5 μM, respectively.

Asiatic acid (AA) derivatives 4 and 5 modified at the C-11 and C-28 positions were designed and synthesized, their structures were confirmed using HRMS, 1 H NMR and 13 C NMR. In vitro antitumor activities of all compounds against MGC-803, NCI-H460, HepG2, Hela and 7404 cancer cell lines were evaluated and compared with commercial anticancer drug 5-fluorouracil (5-FU), employing standard MTT assay. The new compounds 5a – 5t showed stronger anti-proliferative activity than AA, especially compound 5b was found to be the best inhibition activity on HepG2 cell line. In addition, the mechanism of compound 5b was preliminarily investigated by acridine orange/ethidium bromide staining, Hoechst 33258 staining, JC-1 mitochondrial membrane potential staining, flow cytometric, qRT-PCR (quantitative real-time PCR) and Western blot. Compound 5b induced the productions of ROS, and altered anti- and pro-apoptotic proteins, leading to mitochondrial dysfunction and activations of caspase-9 and caspase-3 for causing cell apoptosis. Moreover, the cell cycle analysis showed that compound 5b mainly arrested HepG2 cells in G1 stage.

Chemical investigations of the whole plant ethanol extract of Rubus phoenicolasius led to the isolation and identification of a new pregnane glycoside, 3-O-β-glucopyranosyl-3β,15β-dihydroxypregn-5-en-20-one (1), along with other nine known compounds (2–10). All the isolates were reported from this plant for the first time. The structure of compound 1 was determined by detailed analysis of its spectral data including 1D and 2D NMR. In vitro anti-proliferative activities of compounds 1–3 on MCF-7 and NCI-H460 tumour cell lines were evaluated, and compound 1 was active against the two cell lines with IC50 values of 15.6 and 13.5 μM, respectively.

A series of novel α-aminophosphonate derivatives containing an alizarin moiety (6-7) was designed and synthesized as antitumor agents. MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide) assay results indicated that most compounds exhibited moderate to high inhibitory activity against KB, NCI-H460, HepG 2, A549, MGC-803, Hct-116, CNE and Hela tumor cell lines. The action mechanism of representative compounds 7h, 7j and 7n were investigated by fluorescence staining assays, flow cytometric analysis and real-time polymerase chain reaction (PCR) assays, which indicated that these compounds induced apoptosis and involved G1 phase arrest by increasing the production of intracellular Ca(2+) and reactive oxygen species (ROS) and affecting associated enzymes and genes. The results demonstrated that these compounds may induce apoptosis through a mitochondrion-dependent pathway.

This reaction works with aromatic olefins as nucleophiles giving 1,4-enynes in high yields.

A novel and efficient Cu(OTf)2-catalyzed sp(3)-sp(2) C-C bond formation reaction through the direct coupling of propargylic alcohols with terminal alkenes has been realized under mild conditions. The reaction is tolerant to air and is atom-economical, in accordance with the concept of modern green chemistry. The present protocol provides an attractive approach to a diverse range of 1,4-enynes in high to excellent yields.

Several rhein-phosphonate derivatives (5a–c) 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 compounds 5b exhibited the strongest cytotoxicity against HepG-2 and Spca-2 cells (IC50 was 8.82 and 9.01 µM), respectively. All the synthesized compounds exhibited low cytotoxicity against HUVEC cells. Further experiments proved that 5b could disturb the cell cycle in HepG-2 cells and induce apoptosis. In addition, the binding properties of a model conjugate 5b to DNA were investigated by methods (UV-Vis, fluorescence, CD spectroscopy). Results indicated that 5b showed moderate ability to interact ct-DNA.