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This paper proposed a new definition of community structure from the perspective of the nodes' relative importance. Based on the theory of degree centrality and standardized degree centrality, it mainly researched the evaluation and improvement method on division of community structure in network. The new method could be combined with other community division algorithms to form new community division algorithms. The new method could also be used independently to evaluate and improve the community division results in network. At last, it illustrated the new evaluation and improvement method through MCL algorithm, GN algorithm, Factions algorithm and examples. [ABSTRACT FROM AUTHOR]

Abstract: An efficient and straightforward one-pot strategy for the synthesis of 4,5-dihydropyrazole derivatives from ketones, arylacetylenes, and hydrazines in the presence of KO t Bu/DMSO is described. This strategy provides a flexible and rapid route to polysubstituted 4,5-dihydropyrazoles. [Copyright &y& Elsevier]

Community structure is one of the most important and basic topologic properties of complex network. The rational division of community structure in complex network is the main purpose of the complex network's community division research. This paper mainly researched the division of community structure in complex network based on the theory of supernetwork and standardized degree centrality. Based on the lack of GN algorithm, this paper proposed a new comprehensive algorithm to divide community structure from the perspective of supernetwork. Finally, the new comprehensive algorithm is illustrated through examples. [ABSTRACT FROM AUTHOR]

The catalytic asymmetric Friedel-Crafts alkylation of N-methylindoles with nitroalkenes catalyzed by bifunctional abietic-acid-derived thiourea-ZnII complexes was investigated. Various types of the nitroalkylated indoles were synthesized under mild conditions and obtained with excellent yields (up to 99 %) and good enantioselectivities (up to 86 % ee). These chiral thiourea catalysts are easily available from the commercial abietic acid. [ABSTRACT FROM AUTHOR]

Abstract: An efficient method for palladium-catalyzed Suzuki cross-coupling reaction with simultaneous reduction of nitro- to amino-group has been developed. This method allows nitro-substituted aryl halides to readily react with arylboronic acids, to afford aryl substituted aniline in low to excellent yields. The reaction was catalyzed by Pd(OAc)2 (3mol %) at 150°C under atmospheric pressure in the presence of K2CO3 (3equiv) in DMF/H2O (5/1). [Copyright &y& Elsevier]

A novel and efficient procedure for the synthesis of δ,γ-alkenyl esters with complete E-stereochemistry by the 1,4-addition of alkenes to acrylate esters in the presence of a catalytic amount of palladium chloride has been developed. This method provides a rapid and efficient access to substituted δ,γ-alkenyl esters. [ABSTRACT FROM AUTHOR]

AbstractSesquilignans PD is a natural phenylpropanoid compound that was isolated from Zanthoxylum nitidum var. tomentosum. In this study, we assessed the antitumor effect of PD on SK-Hep-1 and HepG2 cells and the underlying molecular mechanisms. The results revealed that PD markedly inhibited the proliferation and migration of both liver cancer cells. Moreover, PD induced apoptosis, autophagy, and reactive oxygen species (ROS) production in liver cancer cells. Notably, PD increased the protein levels of p-p38 MAPK and p-ERK1/2 in liver cancer cells. This is the first report on the anticancer effect of PD, which is mediated via increased ROS production and MAPK signaling activation. [ABSTRACT FROM AUTHOR]

Peroxisome proliferator-activated receptor alpha (PPARα) and carnitine palmitoyltransferase 1 (CPT1) are important targets of lipid metabolism regulation for nonalcoholic fatty liver disease (NAFLD) therapy. In the present study, a set of novel indole ethylamine derivatives (4, 5, 8, 9) were designed and synthesized. The target product (compound 9) can effectively activate PPARα and CPT1a. Consistently, in vitro assays demonstrated its impact on the lipid accumulation of oleic acid (OA)-induced AML12 cells. Compared with AML12 cells treated only with OA, supplementation with 5, 10, and 20 μM of compound 9 reduced the levels of intracellular triglyceride (by 28.07%, 37.55%, and 51.33%) with greater inhibitory activity relative to the commercial PPARα agonist fenofibrate. Moreover, the compound 9 supplementations upregulated the expression of hormone-sensitive triglyceride lipase (HSL) and adipose triglyceride lipase (ATGL) and upregulated the phosphorylation of acetyl-CoA carboxylase (ACC) related to fatty acid oxidation and lipogenesis. This dual-target compound with lipid metabolism regulatory efficacy may represent a promising type of drug lead for NAFLD therapy. [ABSTRACT FROM AUTHOR]

Environmentally benign electrochemically enabled chemoselective sulfonylation and hydrazination of C2,C3-unsubstituted indoles with arylsulfonyl hydrazide in the presence of ammonium bromide as a redox catalyst and electrolyte have been demonstrated in this work. Under mild electro-oxidation conditions, a series of indole hydrazination products with pharmacological activity were obtained. In vitro, the hydrazination products exhibited a better anti-cancer activity compared with the diazotization products. Further mechanistic studies showed that compound 3ae inhibits cell migration and tubulin aggregation in T-24 cells, thereby leading to cell apoptosis. [ABSTRACT FROM AUTHOR]

A general strategy for the three-component condensation of ketones, hydrazines, and terminal arylalkynes, to give polysubstituted 4,5-dihydropyrazoles, generally in good yields, is presented. [ABSTRACT FROM AUTHOR]

Indoleamine-2,3-dioxygenase 1 (IDO1) and signal transducer and activator of transcription 3 (STAT3) have emerged as significant targets in the tumor microenvironment for cancer therapy. In this study, we synthesized three novel 2-amino-1,4-naphthoquinone amide-oxime derivatives and identified them as dual inhibitors of IDO1 and STAT3. The representative compound NK3 demonstrated effective binding to IDO1 and exhibited good inhibitory activity (hIDO1 IC50 = 0.06 μM), leading to its selection for further investigation. The direct interactions between compound NK3 and IDO1 and STAT3 proteins were confirmed through surface plasmon resonance analysis. A molecular docking study of compound NK3 revealed key interactions between NK3 and IDO1, with the naphthoquinone-oxime moiety coordinating with the heme iron. In the in vitro anticancer assay, compound NK3 displayed potent antitumor activity against selected cancer cell lines and effectively suppressed nuclear translocation of STAT3. Moreover, in vivo assays conducted on CT26 tumor-bearing Balb/c mice and an athymic HepG2 xenograft model revealed that compound NK3 exhibited potent antitumor activity with low toxicity relative to 1-methyl-L-tryptophan (1-MT) and doxorubicin (DOX). Overall, these findings provided evidence that the dual inhibitors of IDO1 and STAT3 may offer a promising avenue for the development of highly effective drug candidates for cancer therapy. [ABSTRACT FROM AUTHOR]

Abstract: A series of dipeptide derivatives from dehydroabietic acid were designed and synthesized as novel antitumor agents. The antitumor activities screening indicated that many compounds showed moderate to high levels of inhibition activities against NCI-H460, HepG2, SK-OV-3, BEL-7404, HeLa and HCT-116 cancer cell lines and that some displayed more potent inhibitory activities than commercial anticancer drug 5-fluorouracil. The mechanism of representative compound 7b was studied by AO/EB staining, Hoechst 33258 staining, JC-1 mitochondrial membrane potential staining, TUNEL assay, DNA ladder assay and flow cytometry, which exhibited that the compound could induce apoptosis in HeLa cells. Further investigation showed that compound 7b induced apoptosis of HeLa cells through a mitochondrial pathway. [Copyright &y& Elsevier]

[Display omitted] Transient receptor potential vanilloid 1 (TRPV1) channel plays an important role in a wide range of physiological and pathological processes, and a comprehensive understanding of TRPV1 gating will create opportunities for therapeutic intervention. Recent incredible advances in cryo-electron microscopy (cryo-EM) have yielded high-resolution structures of all TRPV subtypes (TRPV1–6) and all of them share highly conserved six transmembrane (TM) domains (S1–S6). As revealed by the open structures of TRPV1 in the presence of a bound vanilloid agonist (capsaicin or resiniferatoxin), TM helices S1 to S4 form a bundle that remains quiescent during channel activation, highlighting differences in the gating mechanism of TRPV1 and voltage-gated ion channels. Here, however, we argue that the structural dynamics rather than quiescence of S1–S4 domains is necessary for capsaicin-mediated activation of TRPV1. Using fluorescent unnatural amino acid (flUAA) incorporation and voltage-clamp fluorometry (VCF) analysis, we directly observed allostery of the S1–S4 bundle upon capsaicin binding. Covalent occupation of VCF-identified sites, single-channel recording, cell apoptosis analysis, and exploration of the role of PSFL828, a novel non-vanilloid agonist we identified, have collectively confirmed the essential role of this coordinated S1–S4 motility in capsaicin-mediated activation of TRPV1. This study concludes that, in contrast to cryo-EM structural studies, vanilloid agonists are also required for S1–S4 movement during TRPV1 activation. Redefining the gating process of vanilloid agonists and the discovery of new non-vanilloid agonists will allow the evaluation of new strategies aimed at the development of TRPV1 modulators. [ABSTRACT FROM AUTHOR]

A new acetyl flavonol, named 3-O-acetyl-7-O-methyl kaemferol (1), together with the five known compounds rhamnocitrin (2), rhamnocitrin-3-O-β-d-glucoside (3), rhamnocitrin-4'-β-d-glucoside (4), rhamnazin (5), and p-hydroxyl benzoic acid (6) was isolated from Nervilia fordii (Hance) Schltr. The structures of the compounds were determined by spectroscopic analysis. All the compounds were evaluated against nitric oxide (NO) release, based on the production of NO in mice RAW264.7 stimulated by lipopolysaccharide (LPS). This new compound (1) showed potent inhibitory activity against the production of NO in RAW264.7 stimulated by LPS with the IC50 value of 16.79 μM. [ABSTRACT FROM AUTHOR]

Eight undescribed alkaloids named corydalisine D-K (1 – 7), including one isoquinoline benzopyranone alkaloid (1), one benzocyclopentanone alkaloid (2), four benzofuranone alkaloids (3 , 4 , and 5a / 5b) and two protoberberine alkaloids (6 and 7), along with fourteen known ones, were isolated from the Corydalis saxicola. Their structures, including absolute configurations, were unambiguously identified using spectroscopic techniques, single-crystal X-ray diffraction and electron circular dichroism calculation. Compounds 2 , 14 and 21 exhibit antiproliferative activity against five cancer cell lines. The aporphine alkaloid demethylsonodione (compound 14), which exhibited the best activity (IC 50 = 3.68 ± 0.25 μM), was subjected to further investigation to determine its mechanism of action against the T24 cell line. The molecular mechanism was related to the arrest of cell cycle S-phase, inhibition of CDK2 expression, accumulation of reactive oxygen species (ROS), induction of cell apoptosis, inhibition of cell migration, and activation of p38 MAPK signaling pathway. The results indicated that 14 could be used as a potential candidate agent for further development of anti-bladder transitional cell carcinoma. [Display omitted] • Eight new alkaloids were characterized from the DCM extract of Corydalis saxicola Bunting. • Compound 14 as a CDK2 inhibitor further accelerated apoptotic rate of T24 cells and induced apoptosis by activating the p38 MAPK signaling pathway dependent on the ROS levels. [ABSTRACT FROM AUTHOR]

A metal‐ and oxidant‐free electrochemical method for preparing selenomethyl‐substituted cyclic ethers or lactones via difunctionalization of olefines is presented. A series of selenomethyl‐substituted cyclic ethers, particularly 9‐ and 11‐ membered, selenomethyl‐substituted lactones (4‐6 membered), and selenomethyl‐substituted phthalides can be obtained via this reaction. This method features convenient operation, an electron as oxidant, and ammonium iodide as electrolyte, thereby making it a green synthesis method. [ABSTRACT FROM AUTHOR]

The aerial parts of Tetrastigma hemsleyanum (APTH) have been used as a functional tea in China. The purpose of the current study was to identify the bioactive constituents with inhibitory activity against soluble epoxide hydrolase (sEH) and inducible nitric oxide synthase (iNOS), which are jointly considered potential therapeutic targets for vascular system diseases. In the present study, 39 compounds (1–39) were isolated from the APTH. Among them, compounds 8, 10, 12, 16, 17, 19, and 32 displayed potential activities, with IC50 values ranging from 4.5 to 9.5 µM, respectively, and all in non-competitive inhibition mode. Compounds 5, 10, 12, 19, and 32 displayed potent iNOS inhibitory effects, with IC50 values ranging from 15.6 to 47.3 µM. The results obtained in this work contribute to a better understanding of the pharmacological activities of T. hemsleyanum and its potential application as a functional food. [ABSTRACT FROM AUTHOR]

[Display omitted] • Fifteen new and eight known stilbenes were isolated from Gnetum parvifolium. • Compound 12 is the first stilbene dimer connected through a benzyl group. • Twelve compounds showed significant anti-neuroinflammatory activities. • Compound 10 with the most potent activity was selected for further research. Phytochemical investigation on the aerial parts of Gnetum parvifolium led to the isolation of 15 new and eight known structurally diverse stilbenes. The isolated compounds comprised (E)- or (Z)-stilbene (1 – 6 , 15 – 20), dihydrostilbene (21), phenylbenzofuran (7 , 8 , 22), benzylated stilbene (9 – 11), benzylated stilbene dimer (12), and nitrogen-containing stilbene (13a , 13b , 14) types. The structures of the new compounds (1 – 12 , 13a , 13b , 14) were established through spectroscopic analyses and experimental and calculated ECD data. Compound 12 is the first stilbene dimer connected through a benzyl group. In the anti-neuroinflammatory activity assay, compounds 4 , 5 , 9 – 11 , 13b , and 16 – 21 displayed significant inhibitory effects against LPS-induced NO release in BV-2 microglial cells, with IC 50 values of 0.35–16.1 μM. Compound 10 had the most potent activity (IC 50 = 0.35 μM), and the further research indicated that it could decrease the mRNA levels of iNOS, IL-1 β , IL-6, and TNF- α in a dose-dependent manner. [ABSTRACT FROM AUTHOR]

Nine previously undescribed diisoprenyl-cyclohexene-type meroterpenoids, aspergienynes A-I, together with five known analogues, were obtained from the mangrove endophytic fungal strain Aspergillus sp. GXNU-Y65. The diisoprenyl-cyclohexene-type meroterpenoids were elucidated based on multispectroscopic analysis, and the previously undescribed compounds' absolute configurations were established via electronic circular dichroism calculations. Biological activity results indicated that aspergienyne C (compound 3) had strong anti-nonalcoholic steatohepatitis activity against AML12 cells treated with PA (Palmitic acid) + OA (Oleic acid). At the same concentration of 20 μM, 3 significantly reduced triglyceride (TG) content compared with fenofibrate (positive control) in PA + OA treated AML12 cells, and obviously increased phosphorylation of acetyl-CoA carboxylase. Nine previously undescribed discovered diisoprenyl-cyclohexene-type meroterpenoids, along with five known ones were identified from the mangrove endophytic fungal strain Aspergillus sp. GXNU-Y65. Bioactivity assays revealed that some isolates showed obvious anti-nonalcoholic steatohepatitis activity. [Display omitted] • Nine undescribed meroterpenoids were obtained from Aspergillus sp. GXNU-Y65. • Their structures were established by comprehensive spectroscopic analyses. • Aspergienyne C had strong anti-nonalcoholic steatohepatitis activity in AML12 cells. [ABSTRACT FROM AUTHOR]

A series of diterpene-type compounds were synthesized starting from commercially available (−)-carvone. The Michael reaction of (−)-carvone itself delivered four diastereomeric dimers divergently. Following in parallel transformations of reduction, condensation and reductive amination, the corresponding alcohol, oxime and amine were obtained respectively. Particularly, several cage-like structures were obtained via late-stage olefin functionalization. The absolute configurations of the aforementioned compounds were unambiguously determined by NMR spectral, X-ray crystallographic and conformational analysis. Finally, the in-vitro anti-cancer and anti-inflammatory activities of these dimers were tested preliminarily. [Display omitted] [ABSTRACT FROM AUTHOR]

A new natural product, 3α,19-dihydroxyl-ent-pimara-8(14),15-diene (1), which possesses an α-orientation hydroxymethyl at C-4 and ∆8,14 groups, as well as eight known compounds, was isolated from the rhizomes of Ricinus communis. The structure of 1 was elucidated by extensive spectroscopic methods and its absolute configurations were confirmed by X-ray crystallographic analysis. The inhibitory rate of 1 against protein tyrosine phosphatase 1B (PTP1B) was 49.49% at the concentration of 6.58 × 10−5 mol/L. [ABSTRACT FROM AUTHOR]

Abstract Pentacyclic triterpene derivatives possessing polyhydroxyl ring A exhibit many important pharmacological activities. (1β, 2α, 3β, 19β, 23)−1,2,3,19,23-pentahydroxyolean-12-en-28-oic acid (5), a new bioactive phytochemical with tetra-hydroxyl ring A isolated from Euphorbia sieboldiana in our laboratory, showed potential inhibition effects against several cancer cells previously. This study was performed to investigate the underlying mechanisms of action for its antitumor activity. The results showed that compound 5 inhibited dose-/time-dependently cell growth with low toxicity to normal cells and induced apoptosis in cervical cancer cells. Also, compound 5 inhibited the growth and proliferation of HeLa cells and resulted in G1 phase arrest. Furthermore, exposure of cells to compound 5 caused inactivation of the TNF-α–TAK1–IKK-NF-κB axis and inhibition of TNF-α–stimulated NF-κB activity, followed by down-regulation of NF-κB target genes involved in cell apoptosis (Bcl-2) and in the cell cycle and growth (Cyclin D, c-Myc). Additionally, compound 5 significantly suppressed the migration of HeLa cells. In addition, exposure of HeLa cells to compound 5 decreased the activity of NF-κB through the generation of reactive oxygen species (ROS). Collectively, these results suggested that compound 5 exerted potent anticancer effects on HeLa cells in vitro through targeting the ROS-dependent NF-κB signaling cascade and this compound may be a promising anticancer agent for cancer treatment. Graphical abstract fx1 [ABSTRACT FROM AUTHOR]

A electrochemical method for the synthesis of 3,5‐disubstituted‐1,2,4‐thiadiazoles through NH4I‐mediated dimerization of thioamides is reported. Using the inexpensive NH4I as electrolyte and catalyst, this electrosynthesis approach requires no oxidizing agents and enables the convenient production of diverse 1,2,4‐thiadiazoles products. The approach is an example of S−N bond construction through the electrochemical method. [ABSTRACT FROM AUTHOR]

Abstract Matrix metalloproteinase 9 (MMP-9) is one of the structurally related zinc-dependent endopeptidases families and provides a new target for cancer therapy owing to its pivotal role in metastatic tumors. In this paper, fourteen lignans, including three novel lignans, named selamoellenin B–D (1 – 3), and eleven known lignan derivatives (4 – 14) were isolated from the plant of Selaginella moellendorffii. Among them, compound 3 is optically active, which was enantiomerically seperated to afford a pair of enantiomers, (−)- 3 and (+)- 3. Their structures were elucidated by extensive spectroscopic analyses. Their cytotoxic activities were evaluated against four human cancer cell lines. Among them, five compounds (4 , 5 , 6 , 11 and 13) exhibited great potent cytotoxicity and their structure-activity relationships were also discussed. All compounds except for 3 lignan analogues with low cytotoxicity were selected for further in vitro enzyme inhibition, surface plasmon resonance (SPR), and molecular docking assays based on the MMPs target. The results shown that, compound 11 have the best inhibitory effect and can be considered as a potential drug candidate targeting at MMP-9 for cancer therapy. Graphical abstract Unlabelled Image [ABSTRACT FROM AUTHOR]

Two previous undescribed cyclic pentapeptide-type compounds ( 1 – 2 ), with two known ones ( 3 – 4 ), were first isolated and purified from Clerodendrum japonicum (Thunb.) Sweet. Their structures were elucidated by extensive spectroscopic data (1D and 2D NMR) analysis. The absolute configurations of the two compounds were assigned using a combination of Marfey’s method and HPLC-MS analysis. All four compounds showed weak cytotoxicity against four human cancer cells lines (T24, A549, HepG2, MGC-803), with IC 50 values ranging from 23.8 to 39.6 μM. [ABSTRACT FROM AUTHOR]

A series of inhibitors of NF-κB based on ursolic acid (UA) derivatives containing long-chain diamine moieties were designed and synthesized as well as evaluated the antitumor effects. These compounds exhibited significant inhibitory activity to the NF-κB with IC 50 values at micromolar concentrations in A549 lung cancer cell line. Among them, compound 8c exerted potent activity against the test tumor cell lines including multidrug resistant human cancer lines, with the IC 50 values ranged from 5.22 to 8.95 μM. Moreover, compound 8c successfully suppressed the migration of A549 cells. Related mechanism study indicated compound 8c caused cell cycle arrest at G1 phase and triggered apoptosis in A549 cells through blockage of NF-κB signalling pathway. Molecular docking study revealed that key interactions between 8c and the active site of NF-κB in which the bulky and strongly electrophilic group of long-chain diamine moieties were important for improving activity. [ABSTRACT FROM AUTHOR]

A novel palladium nanoparticle (NP)-metalated porous organic ligand (Pd NPs/POL-xantphos) has been prepared for the chemoselective decarbonylation of aldehydes. This heterogenous catalyst not only has excellent catalytic activity and chemoselectivity, but also holds high activity after 10 runs of reuse. The effective usage of this method is demonstrated through the synthesis of biofuels such as furfuryl alcohol (FFA) via the highly chemoselective decarbonylation of biomass-derived 5-hydroxy-methylfurfural (HMF) with a TON up to 1540. More importantly, 9-fluorenone could be obtained in one step through the decarbonylation of 2-bromobenzaldehyde by using this heterogeneous catalyst. [ABSTRACT FROM AUTHOR]

Cancer metastasis has been a major impediment to effective cancer treatment and is the major cause of cancer-related death. Polyphenols compounds have been reported to possess anti-metastasis activity through their inhibitory activity of matrix metalloproteinases (MMPs). In this paper, twelve polyphenols compounds, including three novel phenols, named selaphenins A–C ( 1 – 3 ), two known selaginellin derivatives ( 4 and 5 ), together with seven known biflavonoids ( 6 – 12 ) were isolated from the plant of Selaginella tamariscina . Their structures were elucidated by extensive spectroscopic analyses. Notably, polyphenols compound 10 suppressed the migration of A549 cells by primary targeting MMP-9. The antitumor activity of compound 10 was possibly due to the induction of cell apoptosis through intrinsic apoptosis pathways, accompanied by increasing the expression of Bax and caspase-3 in a dose-dependent manner. This study provides evidence that polyphenols analogues from S. tamariscina as inhibitors of MMP-9 exhibited potential migration inhibition activities. [ABSTRACT FROM AUTHOR]

Herein, a transition metal-free and efficient cascade reaction of ynones with 2-methylbenzimidazoles under mild conditions has been revealed. This cascade reaction involved a Michael addition/intramolecular cycloaddition/dehydration and provided the desired benzo[4,5]imidazo[1,2-a]pyridines in moderate to good yield. Furthermore, three benzo[4,5]imidazo[1,2-a]pyridines (3d, 3i, and 3q) exhibited good activities against Hep-G2 (human liver cancer), T-24 (human bladder cancer cell), and SK-OV-3 (human ovarian cancer) cell lines with IC50 values in the range of 8.05–10.67 μmol L−1. To investigate the mechanism of the effective inhibition of cell growth, further studies, including cell cycle analysis, apoptosis ratio detection, measurement of Ca2+ generation, ROS, mitochondrial membrane potential assay, and caspase-3/9 activation, were carried out on compound 3i. [ABSTRACT FROM AUTHOR]

Six previously undescribed oleanane-type triterpenoid saponins, fortunosides A–F, together with six known ones, were isolated from the aerial parts of L ysimachia fortunei Maxim. Their structures were established by spectroscopic data analyses (1D, 2D-NMR and HRESIMS) and chemical methods. All isolated triterpenoid saponins were evaluated for their cytotoxicity against four human liver cancer cell lines (SMMC-7721, Hep3B, HuH7, and SK-Hep-1). Three saponins with the aglycone protoprimulagenin A exhibited moderate cytotoxicity against all of the tested human cancer cell lines, with IC 50 values ranging from 4.76 to 15.12 μM. [ABSTRACT FROM AUTHOR]

Five previously undescribed monoterpenoid indole alkaloids, mappianines A−E, along with twelve known analogues, were isolated from the stems of Mappianthus iodoides Hand.-Mazz. Their structures and absolute configurations were determined by spectroscopic analysis, single-crystal X-ray diffraction, and ECD calculations. The plausible biogenetic pathway of mappianine A was proposed. All the isolated compounds were evaluated for their cytotoxic effects on MGC-803, Bel-7404, A549, NCI-H460, and HepG2 cancer cell lines. Mappianine B, tetrahydroalstonine, β -carbolin-1-one, and 1,2,3,4-tetrahydronorharman-1-one displayed moderate cytotoxicity against all cell lines tested, with IC 50 values ranging from 5.19 to 42.86 μ M. [ABSTRACT FROM AUTHOR]

Twelve pairs of sesquineolignan enantiomers (1a / 1b − 6a / 6b and 1c / 1d − 6c / 6d), including twenty one undescribed and three known (2b , 3b , and 4b) sesquineolignans were isolated from an ethanol extract of the stems and leaves of Neoshirakia japonica (Euphorbiaceae). The successful separation of twelve pairs of enantiomers with mirror image-like electronic circular dichroism (ECD) curves and opposite specific rotation values, as one of the most important steps in compound isolation, was carried out by chiral HPLC columns. The absolute configurations of all undescribed sesquineolignans were elucidated by comprehensive analysis of their experimental ECD spectra. The effects of all the isolates on antineuroinflammatory and radical scavenging activity were evaluated. Compared with the positive control minocycline (IC 50 = 1.2 μM), compounds 1a / 1b / 1c / 1d − 6a / 6b / 6c / 6d with IC 50 values being greater than 50 μM displayed almost no effect on the inhibition of NO production in LPS-induced BV-2 microglial cells. The results of DPPH-radical scavenging activity for them showed that compound 3c had moderate radical scavenging ability (EC 50 = 48.47 μM), while the EC 50 value of positive control vitamin C was 18.21 μM. Twelve pairs of sesquineolignan enantiomers, including twenty one undescribed and three known sesquineolignans were isolated from Neoshirakia japonica. The effects of all the sesquineolignans on antineuroinflammatory and antioxidant activities were evaluated. [Display omitted] • Twelve pairs of sesquineolignan enantiomers were isolated from Neoshirakia japonica. • The separation of these enantiomers were carried out successfully by chiral HPLC columns. • The absolute configurations of all sesquineolignans were established by analysis of their ECD spectra. [ABSTRACT FROM AUTHOR]

An efficient and selective approach to the synthesis of selenide ethers containing one or two geminal C-Se bonds from readily available diselenides and phenylacetic acids was developed. Compounds containing one C-Se bond were prepared by employing air as the oxidant under metal-free conditions, whereas compounds having two geminal C-Se bonds were formed via the iron(III) chloride/oxygen/cesium carbonate (FeCl3/O2/Cs2CO3) system. Moreover, 1,2-diphenyldisulfane also could be smoothly converted into the corresponding sulfur ether product under the standard reaction conditions. [ABSTRACT FROM AUTHOR]

An unexpected domino reaction of β-keto sulfones with acetylene ketones has been developed. The domino reaction of β-keto sulfones with diynones proceeded smoothly in the presence of 30 mol% K2CO3 without other additives, and afforded the novel 3(2 H)-furanone derivatives. On replacing the diynones with terminal alkyne ketones, the reaction regioselectivity was changed and sulfonylbenzenes were obtained via benzannulation in good yields. [ABSTRACT FROM AUTHOR]

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 IC 50 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. [ABSTRACT FROM AUTHOR]

Eleven oleanane-type triterpenoid saponins, foegraecumosides A–K, and eight known ones, were isolated from the aerial parts of Lysimachia foenum-graecum . Their structures were elucidated by spectroscopic data analyses and chemical methods. All isolated saponins were evaluated for their cytotoxicity against four human cancer cell lines (NCI-H460, MGC-803, HepG2, and T24). Seven saponins containing the aglycone cyclamiretin A exhibited moderate cytotoxicity against all tested human cancer cell lines, with IC 50 values of 9.3–24.5 μM. Simultaneously, the cytotoxic activities of foegraecumosides A and B, lysichriside A, ardisiacrispins A and B, cyclaminorin, and 3 -O - α -L-rhamnopyranosyl-(1 → 2)- β - d -glucopyranosyl-(1 → 4)- α - l -arabinopyranosyl-cyclamiretin A were tested on drug-resistant lung cancer cell lines (A549 and A549/CDDP, respectively). Ardisiacrispin B displayed moderate cytotoxicity against A549/CDDP, with an IC 50 value of 8.7 μM and a resistant factor (RF) of 0.9. [ABSTRACT FROM AUTHOR]

Benzyl bromides bearing an ortho-substituted α,β-unsaturated ketone moiety are found to be promising precursors for the synthesis of fused 1,2,3-triazole and isoindoline derivatives via an intramolecular azide–alkene cascade reaction under catalyst free conditions. Fused 1,2,3-triazole derivatives 2 were synthesized in excellent yields by treating compounds 1 with sodium azide in DMF at room temperature, whereas isoindoline derivatives 3 were produced in moderate to good yields only by slight modification of the reaction conditions. Both reactions call for simple and mild conditions, display broad substrate scopes and result in good regiospecificity. [ABSTRACT FROM AUTHOR]

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 IC 50 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. [ABSTRACT FROM AUTHOR]

[Display omitted] • Seven new tetrahydrofuran lignans with unusual isopentenyl substitutions, along with 14 known ones, were isolated from Zanthoxylum nitidum. • Tetrahydrofuran-core lignan 3 showed higher activity than furan-core lignan 4 in osimertinib-resistant non-small cell lung cancer cells. • Compound 3 suppressed the c-Met/JAK1/STAT3 and PI3K/AKT/mTOR signaling pathway in the HCC827-osi cells. • Osimertinib and 3 exhibited synergistic anticancer effects in HCC827-osi cells, and 3 suppressed STAT3 protein level stronger than osimertinib. Seven previously undescribed tetrahydrofuran lignans with different configurations and unusual isopentenyl substitutions, nitidumlignans D-J (corresponding to compounds 1 , 2 , 4 , 6 , 7 , 9 and 10), along with 14 known lignans, were isolated from Zanthoxylum nitidum. Notably, compound 4 is an uncommon naturally occurring furan-core lignan derived from tetrahydrofuran aromatization. The antiproliferation activity of the isolated compounds (1 – 21) was determined in various human cancer cell lines. The structure–activity study revealed that the steric positioning and chirality of the lignans exert important effects on their activity and selectivity. In particular, compound 3 (sesaminone) exhibited potent antiproliferative activity in cancer cells, including acquired osimertinib-resistant non-small-cell lung cancer (HCC827-osi) cells. Compound 3 also inhibited colony formation and induced the apoptotic death of HCC827-osi cells. The underlying molecular mechanisms revealed that 3 downregulated the activation of the c-Met/JAK1/STAT3 and PI3K/AKT/mTOR signaling pathways in the HCC827-osi cells. In addition, the combination of 3 and osimertinib exhibited synergistic effects on the antiproliferative activity against HCC827-osi cells. Overall, these findings inform the structure elucidation of novel lignans isolated from Z. nitidum, and sesaminone was identified as a potential compound for exerting antiproliferative effects on osimertinib-resistant lung cancer cells. [ABSTRACT FROM AUTHOR]

[Display omitted] A series of 2-oximino-2-indolylacetamide derivatives were designed, synthesized and evaluated for their antitumour effects. Among them, 4d exhibited the most potent antiproliferative effect in vitro on the tested human cancer cells. Additionally, 4d significantly induced cell apoptosis, caused mitochondrial dysfunction, promoted Bax, cleaved-PARP and p53 expression and inhibited Bcl-2 expression in 5-8F cells. Moreover, 4d remarkably promoted autophagosome formation, leading to cell apoptosis. Further investigation indicated that 4d could trigger cell death through cell ferroptosis, including increased ROS generation and lipid peroxidation and decreased glutathione peroxidase 4 (GPx4) expression and glutathione (GSH) levels. More importantly, 4d induced 5-8F cell death by activating ROS/MAPK and inhibiting the AKT/mTOR and STAT3 signalling pathways. Interestingly, 4d significantly suppressed tumour growth in a 5-8F cell xenograft model without obvious toxicity to mice. Overall, these results demonstrate that 4d may be a potential compound for cancer therapy. [ABSTRACT FROM AUTHOR]

Five pairs of new racemic alkamides (1a/1b and 4a/4b - 7a/7b) and two new achiral derivatives (2 – 3), as well as five known ones (8 – 12), were purified from the 95% EtOH extract of Zanthoxylum nitidum. Their structures were elucidated based on spectroscopic analyses (NMR and HR-ESI-MS), electronic circular dichroism (ECD) and NMR calculations. The enantiomeric separation was successfully achieved by chiral-phase HPLC-ECD measurements. Among all the isolates, compounds 2 , 3 , and 10 showed inhibitory effects against five human cancer cell lines, with IC 50 values in range of 18.51–48.03 μM. [Display omitted] • Seven new unsaturated alkylamide derivatives were isolated from Zanthoxylum nitidum. • The absolute configurations were determined by ECD calculation. • The enantiomeric separation was successfully achieved by chiral-phase HPLC-ECD measurements. • Compounds 2 , 3 , and 10 displayed moderate inhibitory effects against five human cancer cell lines. [ABSTRACT FROM AUTHOR]

Eleven previously undescribed alkaloids, including three pairs of enantiomers nitidumalkaloids A–C, a pair of scalemic mixtures nitidumalkaloid D and three optically pure or achiral alkaloids, nitidumalkaloids E–G, along with 20 known alkaloids, were isolated from an ethanolic extract of the whole Zanthoxylum nitidum (Roxb.) DC plant. The chemical structures of the alkaloids were elucidated using a combination of comprehensive nuclear magnetic resonance (NMR) and high-resolution electro-spray ionization mass spectrometry (HR-ESI-MS) analyses. The configuration of the stereogenic centers of all undescribed compounds was precisely established based on single-crystal X-ray diffraction and electronic circular dichroism (ECD) calculations. Racemic mixtures of nitidumalkaloids A–D were purified, and their enantiomers were analyzed via chiral-phase high-performance liquid chromatography with electrochemical detection measurements (HPLC-ECD). Twelve compounds exhibited significant antiproliferative activities against a panel of cancer cell lines. Further studies were designed to investigate the underlying molecular mechanism of (1′ S , 6 R)-nitidumalkaloid B, which was the most active antiproliferative agent against human cancer A549 cells. G2/M cell cycle arrest, induction of apoptosis, and suppression of the Wnt/β-catenin signaling pathway were in part associated with the antiproliferative activity of (1′ S , 6 R)-nitidumalkaloid B. Moreover, (1′ S , 6 R)-nitidumalkaloid B inhibited cell migration by downregulating the epithelial-mesenchymal transition process in A549 cells. These data suggest that the antiproliferation activity of (1′ S , 6 R)-nitidumalkaloid B was correlated with the stereoselectivity of the stereoisomers, and (1′ S , 6 R)-nitidumalkaloid B was prioritized as a potential leading compound for the management of aggressive human non-small-cell lung cancer (NSCLC) from natural products. Eleven previously undescribed alkaloids, along with 20 known alkaloids, were isolated from Zanthoxylum nitidum. Compound 2b exhibited anti-proliferative activities against the A549 cells by suppressed the Wnt/β-catenin signaling pathway and the EMT process. [Display omitted] • Eleven undescribed and twenty known alkaloids were isolated from Zanthoxylum nitidum. • Their structures were established by comprehensive spectroscopic analyses. • Four stereoisomers revealed strongly antiproliferative activity for lung cancer cell lines. • Compound 2b suppressed the Wnt/β-catenin signaling pathway and the EMT process in the A549 cells. [ABSTRACT FROM AUTHOR]

A diagram is presented which illustrates indolizines synthesis from 2-alkylazaarenes.

C1-Benzoyl isoquinolines can be generated via a palladium(ii)-catalyzed C–C and C–O coupling of isoquinoline N-oxides with aromatic nitroalkenes. The reaction proceeds through remote C–H bond activation and subsequent intramolecular oxygen atom transfer (OAT). In this reaction, the N–O bond was designed as a directing group in the C–H bond activation as well as the source of an oxygen atom. [ABSTRACT FROM AUTHOR]

A transition metal-free and efficient method for the synthesis of 3-alkynylpyrrole-2-carboxylates from diynones and glycine esters or 2-aminoacetophenone hydrochloride has been developed. This transformation provides a large range of substituted pyrroles in good to excellent yields with the elimination of water as the only by-product. The detailed mechanistic studies elucidated that this transformation involves a Michael addition/intramolecular cyclodehydration process. [ABSTRACT FROM AUTHOR]

A new cytisine-type alkaloid, (−)-N-hexanoylcytisine (1), and a new isoflavan, (3S, 4R)-4-hydroxy-7,4′-dimethoxyisoflavan 3′-O-β-d-glucopyranoside (2), along with 10 known compounds, were isolated from the rhizomes ofSophora tonkinensis. Their structures were determined by spectroscopic methods, chemical evidence, and ECD data analysis. All of the isolates were evaluated for their cytotoxic activities against four human tumor cell lines. [ABSTRACT FROM AUTHOR]

Through a structure-based molecular hybridization approach, a series of novel quinazolinyl-diaryl urea derivatives were designed, synthesized, and screened for their in vitro antiproliferative activities against three cancer cell lines (HepG2, MGC-803, and A549). Six compounds ( 7g , 7m , 7o , 8e , 8g , and 8m ) showed stronger activity against a certain cell line compared with the positive reference drugs sorafenib and gefitinib. Among the six compounds, 8g exhibited the strongest activity. In particular, compound 8g induced A549 apoptosis, arrested cell cycle at the G0/G1 phase, elevated intracellular reactive oxygen species level, and decreased mitochondrial membrane potential. This compound can also effectively regulate the expression of apoptosis- and cell cycle-related proteins, and influence the Raf/MEK/ERK pathway. Molecular docking and structure–activity relationship analyses revealed that it can bind well to the active site of the receptor c-Raf, which was consistent with the biological data. Therefore, compound 8g may be a potent antitumor agent, representing a promising lead for further optimization. [ABSTRACT FROM AUTHOR]

The chemical investigation on Corydalis balansae resulted in the isolation of three previous undescribed compounds (1 , 10 , and 11) and 17 known compounds. Compound 1 and 2 were obtained as two lignanamide dimers, and compound 11 had a spiro [benzofuranone-benzazepine] skeleton, which was found in Corydalis for the first time. The structures of new compound were determined by the detailed analysis of 1D/2D NMR, UV, and IR data. Absolute configurations of compounds 10 and 11 were defined by their crystal X-ray diffraction data and calculations of electronic circular dichroism (ECD). The CCK-8 method was used to assay the inhibition effect of all the compounds on the growth of Hela, MGC-803, A549, and HepG2 cancer cells. Compound 2 , 13 , and 14 showed moderate inhibitory activity against the tested cell lines. Compound 2 exhibited potential antitumor activity against MGC-803 cells with an IC 50 value of 20.8 μM, while the positive control etoposide was 17.3 μM. Furthermore, results from the cellular-mechanism investigation indicated that compound 2 could induce S-phase cell-cycle arrest and MGC-803 cells apoptosis, which was triggered by the up-regulation of PARP1, caspase-3 and -9, Bax, and down-regulation of Bcl-2. The 2 -induced strong apoptosis indicated that compound 2 had good potential as an antitumor lead compound. [Display omitted] [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 (IC 50 ) 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. [ABSTRACT FROM AUTHOR]