Abnormal functional hubs in migraine patients: a resting-state MRI analysis about voxel-wise degree centrality.

The purpose was to explore the spatial centrality of the whole brain functional network related to migraine and to investigate the potential functional hubs associated with migraine. 32 migraine patients and 55 healthy controls were recruited and they received resting-state functional magnetic resonance imaging voluntarily. Voxel-wise Degree Centrality (DC) was measured across the whole brain, and group differences in DC were compared.

Design, Synthesis, and Anticancer Activity of Cinnamoylated Barbituric Acid Derivatives.

This work deals with the design and synthesis of 18 barbituric acid derivatives bearing 1,3-dimethylbarbituric acid and cinnamic acid scaffolds to find potent anticancer agents. The target molecules were obtained through Knoevenagel condensation and acylation reaction. The cytotoxicity was assessed by the MTT assay.

Piperlongumine Analogs Promote A549 Cell Apoptosis through Enhancing ROS Generation.

Chemotherapeutic agents, which contain the Michael acceptor, are potent anticancer molecules by promoting intracellular reactive oxygen species (ROS) generation. In this study, we synthesized a panel of (piperlongumine) analogs with chlorine attaching at C2 and an electron-withdrawing/electron-donating group attaching to the aromatic ring. The results displayed that the strong electrophilicity group at the C2-C3 double bond of PL analogs plays an important role in the cytotoxicity whereas the electric effect of substituents, which attached to the aromatic ring, partly contributed to the anticancer activity.

The potential role of the 5,6-dihydropyridin-2(1)-one unit of piperlongumine on the anticancer activity.

Piperlongumine (PL), a potent anticancer agent from the plant long pepper (), contains the 5,6-dihydropyridin-2(1)-one heterocyclic scaffold and cinnamoyl unit. In this paper, we synthesized a series of PL analogs and evaluated their cytotoxicity against cancer cells for the sake of exploring which pharmacophore plays a more potent role in enhancing the anticancer activities of PL. These results illustrated that the position effect, not the electronic effect, of substituents plays a certain role in the cytotoxicity of PL and its analogs.

Synthesis and biological evaluation of β-ionone oriented proapoptosis agents by enhancing the ROS generation.

β-ionone, a cyclic terpenoid compound present in many fruits, has been showed a broad spectrum of biological activities. In this paper, we synthesized a panel of β-ionone derivatives and tested their anti-proliferation activity on cancer cell by the MTT assay. The results showed that most of the β-ionone derivatives were more active than β-ionone and curcumin.

Synthesis and evaluation of the anticancer activity of bischalcone analogs in human lung carcinoma (A549) cell line.

Bischalcone has gained much attention because of its wide range of application in pharmaceutical chemistry. This work aims to evaluate the antiproliferation effects and explore the anticancer mechanism of bischalcone analogs on human lung cancer A549 cells. In this study, we synthesized a series of bischalcone analogs via Aldol condensation reaction; MTT method was used to evaluate the antiproliferation effects; the 2',7'-dichlorofluorescein fluorescence assay was used to determine the intracellular reactive oxygen species levels; the glutathione reductase-DTNB recycling assay was used to detect the redox imbalance; determination of thiobarbituric acid-reactive substance was used to evaluate the lipid peroxidation; Rhodamine 123 was used to test the mitochondrial membrane potential (MMP); the FITC/PI kit was used to detect the apoptosis; Western blotting was used to detect the expression of Bax and Caspase 3.

2,2'-Fluorine mono-carbonyl curcumin induce reactive oxygen species-Mediated apoptosis in Human lung cancer NCI-H460 cells.

In this paper, we synthesized three fluorine-substituted mono-carbonyl curcumin analogs and evaluated their cytotoxicity against several cancer cells by the MTT assay. The results exhibited that all the three compounds were more active than the leading curcumin. Especially, 2,2'-F mono-carbonyl curcumin, 1a, surfaced as an important lead compound displaying almost 4-fold cytotoxicity relative to curcumin.

3,3'-OH curcumin causes apoptosis in HepG2 cells through ROS-mediated pathway.

In this paper, we synthesized a series of curcumin analogs and evaluated their cytotoxicity against HepG2 cells. The results exhibited that the hydroxyl group at 3,3'-position play an essential role in enhancing their anti-proliferation activity. More importantly, 3,3'-hydroxy curcumin (1b) caused apoptosis in HepG2 cells with the ROS generation, which may be mainly composed of hydroxyl radicals (HO) and H2O2.

Insights into the importance for designing curcumin-inspired anticancer agents by a prooxidant strategy: The case of diarylpentanoids.

Developing anticancer agents by a prooxidant strategy has attracted increasing attention in recent years, although it is not conventional in medicinal chemistry and is completely opposite to antioxidant therapy. In this work, a panel of diarylpentanoids as the curcumin mono-carbonyl analogs were designed and synthesized, and their cytotoxic and proapoptotic mechanisms against human lung cancer A549 cells were investigated at the frontiers of chemistry and biology. It was found that compared with curcumin, the compounds (A1, B1, and C1) bearing two ortho substituents on the aromatic rings, especially A1, exhibit significantly increased cytotoxic and proapoptotic activities through a Michael acceptor unit-dependent prooxidant-mediated mechanism.

Synthesis and antioxidant activity of hydroxylated phenanthrenes as cis-restricted resveratrol analogues.

Five hydroxylated phenanthrenes as "cis-configuration-fixed" resveratrol analogues differing in the number and position of the hydroxyl groups were designed and synthesized. Their antioxidant activity was studied by ferric reducing antioxidant power, 2,2-diphenyl-1-picrylhydrazyl free radical-scavenging, and DNA strand breakage-inhibiting assays, corresponding to their electron-donating, hydrogen-transfer and DNA-protecting abilities, respectively. In the above assays, their activity depends significantly on the number and position of the hydroxyl groups, and most of them are more effective than resveratrol.

CuII ions and the stilbene-chroman hybrid with a catechol moiety synergistically induced DNA damage, and cell cycle arrest and apoptosis of HepG2 cells: an interesting acid/base-promoted prooxidant reaction.

Development of potential cancer treatment strategies by using an exogenous reactive oxygen species (ROS)-generating agent (prooxidant) or redox intervention, has attracted much interest. One effective ROS generation method is to construct a prooxidant system by polyphenolic compounds and Cu(II) ions. This work demonstrates that Cu(II) and the stilbene-chroman hybrid with a catechol moiety could synergistically induce pBR322 plasmid DNA damage, as well as cell cycle arrest and apoptosis of HepG2 cells.

Extraordinary radical scavengers: 4-mercaptostilbenes.

In the past decade, there was a great deal of interest and excitement in developing more active antioxidants and cancer chemoprevention agents than resveratrol, a naturally occurring stilbene. In this work, eight resveratrol-directed 4-mercaptostilbenes were constructed based on the inspiration that thiophenol should be a stronger radical scavenger than phenol, and their reaction rates with galvinoxyl (GO(.)) and 2,2-diphenyl-1-picrylhydrazyl (DPPH(.

Synthesis and biological evaluation of hydroxylated 3-phenylcoumarins as antioxidants and antiproliferative agents.

Based on the observed biological activities of coumarins and resveratrol, we synthesized fourteen hydroxylated 3-phenylcoumarins (stilbene-coumarin hybrids) including six novel ortho-hydroxy-methoxy substituted derivatives, 1-14, by Perkin reaction. We characterized these compounds concerning their antioxidant activity against 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH)-induced pBR322 DNA strand breakage, and their antiproliferative effects on human promyelocytic leukemia HL-60 and human lung adenocarcinoma epithelial A549 cells. Structure-activity relationship information suggests that the introduction of ortho-hydroxy-methoxy groups and ortho-dihydroxy groups on the aromatic A ring could efficiently improve antiproliferative activity.