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A colorimetric and turn-on fluorescent chemodosimeter 1 based on diaminomaleonitrile was synthesized for Cu2+ detection. It showed high selectivity and sensitivity towards Cu2+ over the other tested metal ions. Probe 1 in acetonitrile exhibited a strong absorption band at 530 nm and weak fluorescence emission when excited at 480 nm, while the addition of Cu2+ could lead to a 30-nm blue shift of the absorption band and a remarkable fluorescence enhancement. Moreover, the detection limit of probe 1 for Cu2+ was calculated to be 28 nM. Quite different from the reported mechanism based on a metal-complexation induced fluorescence enhancement, the sensing mechanism was proved to be based on the Cu2+-promoted hydrolysis reaction, which was confirmed by 1H NMR, 13C NMR and mass spectrum analysis. Studies on probe 2 were carried out to verify the universality of this sensing mechanism.

Fe3+ ions play an important role in both biological and environmental field. In this work, two novel rhodamine-based colorimetric and fluorescent probes (RBA2 and RBA3) were designed and synthesized for the efficient detection of Fe3+. Upon the addition of Fe3+, the fluorescence intensity of RBA2 and RBA3 enhanced 108-fold and 222-fold, respectively. RBA2 and RBA3 exhibited a low detection limit which could achieve 12.8 nM and 11.0 nM. In addition, the binding modes of RBA2 and RBA3 with Fe3+ were proved to be 1:1 stoichiometry in the complexes by Job's plot, ESI-MS and 1H NMR results. The complexing ability of RBA3 with Fe3+ excessed to that of RBA2 that was determined by the binding association constants, and highly consistent with DFT calculations results. Furthermore, RBA2 and RBA3 were further utilized to detect Fe3+ in living cells and real water samples, indicating their promising prospects in biological and environmental field.

A sensitive enzyme-linked immunosorbent assay (ELISA) has been developed based on the dual catalysis of dendritic Pd-Pt porous nanoparticles and horseradish peroxidase (HRP). The Pd-Pt porous nanoparticles, for the first time, were used to immobilize HRP. As a proof-of-concept demonstration, HRP functioned Pd-Pt porous nanoparticles were applied in hCG detection with a detection limit of 0.07 IU L−1. The linear intervals is 0.1–6.4 IU L-1. The Pd-Pt-HRP possesses a better sensitivity than the traditional BA-ELISA. Furthermore, the precision and reproducibility and selectivity were assessed to be eligible for the hCG monitoring.

Lycium barbarum have received an increasing popularity due to its powerful biological activity and medicinal use. However, the effect of Lycium barbarum on skin remains largely uncharacterized. The general purpose of this paper was to characterize the phenolic compounds in Lycium barbarum extract (LBE) using LC-HRMS/QTOF method and to investigate whether topical administration of LBE can repair skin barrier dysfunction in mice. Our data demonstrated that LBE could not only decrease ROS level and matrix metalloproteinase expression, but also strengthen intrinsic antioxidant defense system including SOD, GSH-Px and CAT, thereby resulting in increased skin collagen content and an improvement of UV-induced skin erythema, thickness and wrinkles. Improved skin barrier functions were highly correlated with increased expression of filaggrin, involucrin and loricrin as well as antioxidant proteins such as Nrf2 and HO-1 in UV-irradiated mice, suggesting that LBE may be promising natural products at a lower cost for the topical application in the treatment of skin diseases with defective barrier function.

The effect of a series of triarylamine based D-pi-A organic dyes, namely RK1, BA504, BA741 and the simple L1 reference dye on solid-state dye sensitized solar cells (s-DSSCs) performances was studied. The solid hole transporting material (HTM) was obtained by in-situ photoelectrochemical polymerization (in-situ PEP) process applied in two different media (water and acetonitrile) to produce the poly-3,4 ethylenedioxythiophene (PEDOT) conducting polymer (CP). A joint experimental and theoretical (density functional theory and time-dependent density functional theory) study is conducted to correlate the dye molecular structure containing different donor, pi-bridge or acceptor with several physicochemical characteristics such as optical (absorption and emission), electronic and redox properties of dyes in organic and aqueous medium; in-situ PEP process and charge transfer kinetics at the DSSC interfaces (Dye/TiO2 and Dye/HTM) through the alignment of the different energy levels of the dyes and electrodes. These properties are considered since they govern the performance of s-DSSCs denoted by the short-circuit current (J(sc)), open circuit cell potential (V-oc) and fill factor (FF). Among the four studied dyes, the s-DSSCs based on RK1, shows the best power conversion efficiency of 1.75% resulting from highest FF (0.57), V-oc (550 mV) and J(sc) (5.6 mA/cm(2)). The large differences in experimental photovoltaic performances of the obtained s-DSSCs have been well outlined and provide the guidelines for future development of more efficient solar-cell sensitizers.

Background Despite Tricholoma matsutake has been used as natural health products with multiple medicinal properties, detailed information about its polyphenolic composition as sources of anti-photoaging agents remains to be determined. Objective To investigate the impact of polyphenols extracted from Tricholoma matsutake (TME) on Ultraviolet B (UVB)-induced skin photoaging. Materials and methods Various factors of oxidative stress and inflammation as well as histological and immunohistochemical analysis in the mouse dorsal skin were determined after UVB radiation. Results Topical administration with TME suppressed the UVB-induced skin thickness, wrinkles and erythema, and increased skin collagen content. Furthermore, TME decreased reactive oxygen species (ROS) level, upregulated glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT) and glucose-6-phosphate dehydrogenase (G6PDH) activities and inhibited the expression of IL-1, IL-6, IL-8 and TNF-α in mice irradiated with UVB. TME could reduce UVB-induced p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation and effectively inhibited the activity of the transcriptional factor nuclear factor-kappa B (NF-κB), thereby reducing the cyclooxygenase-2 (COX-2) expression, which is an important mediator of inflammatory cascade leading to the inflammatory response. Conclusion Our data demonstrated that TME had various beneficial effects on UVB-induced skin photoaging due to its antioxidant and anti-inflammatory activities, and it might be exploited as a promising natural product in skin care, anti-photoaging and the therapeutic intervention of skin disorders related to both oxidative stress and inflammation.

Dry eye disease (DED) is characterized by increased osmolality of tears due to a lack of production or increased evaporation of tears. Hyperosmolarity is involved in DED pathogenesis, which damages ocular surface cells and leads to inflammation of the ocular surface. We investigated the anti-inflammatory effect of paeoniflorin (PF) from Paeonia lactiflora Pall. on human corneal epithelial (HCE) cells and its molecular mechanisms, and its therapeutic effects on a mouse model of experimental dry eye (EDE). HCE cells were treated with PF-1 (PF prepared in vitro; 0.01%, 0.1% and 1.0%). Protein production/activity was determined by Western blotting, RT-PCR and immunofluorescent staining. Meanwhile, eye drops containing 0.01%, 0.1% and 1.0% of PF-2 (PF prepared in vivo) were applied to the EDE, and the tear volume, corneal fluorescein-staining score, detachment of the corneal epithelium, and immunohistochemical staining were measured after 28 days of treatment. PF reduced expression of proinflammatory factors such as interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-α in HCE cells, and significantly improved dry-eye signs, including tear volume, desquamation of the corneal epithelium and ocular surface inflammation in mice treated with 1.0% PF-2. Further study showed that PF improved EDE by inhibiting mitogen-activated protein kinase (MAPK), phosphorylated (p)-c-Jun N-terminal kinase (JNK) and pp-38, and nuclear factor kappa B (NF-κB) signaling pathways. These data suggest that PF can improve dry-eye symptoms and reduce expression of proinflammatory mediators. Hence, eye drops containing PF could be used as an adjunctive treatment for DED.

Amplifying the signal of ELISA is important in the early disease diagnosis. Herein we report an ultrasensitive ELISA applying for the detection of hCG based on the assemble of AuNPs induced by functional PAMAM. The AuNP-PAMAM probe shows a competitive advantage sensitivity of 0.03 IU L-1 compared to traditional ELISA and mAb1-AuNP-HRP probe. The line range is ranged from 0.1 to 6.4 IU L-1. Moreover, the precision and reproducibility and specificity of AuNP-PAMAM probe are also eligible for the detection of hCG. The assembled AuNPs was firstly used in the signal enhancement in immunoassay.

Psoriasis is a usual immune-mediated inflammatory skin disease with undefined pathogenesis. Aromatic-turmerone (ATM) is a mainly constituent of essential oil from Curcuma longa L. It has been shown to exhibit strong anti-oxidant, anti-tumor activities and anti-inflammatory effects. In this study, we investigated the effects of ATM on imiquimod (IMQ)-induced psoriasis-like BALB/c mice and its molecular mechanisms for anti-inflammatory effect. ATM showed inhibition of the transfer of CD8+ T cells in epidermis, and reduced expression of NF-κB and COX-2 as well as phosphorylation of p38 MAPK. It also decreased the level of TNF-α and IL-6, and down-regulates IL-17 IL-22 and IL-23 mRNA synthesis. Notably, we demonstrated that topically applied ATM alleviated skin inflammation in IMQ-induced mice. These results indicate that ATM, a natural active compound exhibits anti-inflammatory activity and is a promising candidate molecule to treat inflammatory skin diseases, such as psoriasis.

In this study, a series of carbazole-rhodanine conjugates was synthesized and evaluated for their Topoisomerase II inhibition potency as well as cytotoxicity against a panel of four human cancer cell lines. Among these thirteen compounds, 3a, 3b, 3g, and 3h possessed Topoisomerase II inhibition potency at 20 μM. Mechanism study revealed that these compounds may function as Topo II catalytic inhibitors. It was found that the electron-withdrawing groups on the phenyl ring of compounds played an important role on enhancing both enzyme inhibition and cytotoxicity.

A novel metal-free organic dye based on triarylamine functionalized by a carbazole unit is synthesized and used in solid state dye sensitized solar cells (sDSC). The carbazole is co-polymerized with bis-EDOT by in-situ photo-electrochemical polymerization leading to a hole transporting polymer material covalently bonded to the light active centre. These first photovoltaic performances results are promising in sDSCs applications.

A novel BODIPY-hemicyanine based fluorescent probe 1 for cyanide (CN − ) detection was designed and synthesized. Among the tested anions, the probe showed high selectivity towards CN − . Only addition of CN − to probe 1 in aqueous solution (V H2O /V EtOH = 1/1) could result in a remarkable blue shift of the absorption band from 385 nm to 265 nm and induce 20-fold fluorescence enhancement at 515 nm. The sensing mechanism was based on nucleophilic addition between CN − and indolium group, which was confirmed by 1 H NMR and mass spectrum analysis. Plot of fluorescence intensity as a function of CN − concentrations exhibited a good linear relationship in the range of 0–10 μM, with a detection limit to be 1.53 ppb. Moreover, the proposed sensing approach could work in a wide pH range from 5.0–9.0 and reach an equilibrium instantaneously. Finally, probe 1 was successfully applied in detection of CN − in natural water samples and on test paper strips with satisfactory results.

International audience; Protein-protein interactions (PPIs) are well recognized as promising therapeutic targets. Consequently, interfering peptides (IPs) - natural or synthetic peptides capable of interfering with PPIs - are receiving increasing attention. Given their physicochemical characteristics, IPs seem better suited than small molecules to interfere with the large surfaces implicated in PPIs. Progress on peptide administration, stability, biodelivery and safety are also encouraging the interest in peptide drug development. The concept of IPs has been validated for several PPIs, generating great expectations for their therapeutic potential. Here, we describe approaches and methods useful for IPs identification and in silico, physicochemical and biological-based strategies for their design and optimization. Selected promising in-vivo-validated examples are described and advantages, limitations and potential of IPs as therapeutic tools are discussed.

In this study, a series of benzimidazole–rhodanine conjugates were designed, synthesized and investigated for their topoisomerase II (Topo II) inhibitory and cytotoxic activities. The results from Topo II-mediated pBR322 DNA relaxation and cleavage assays showed that the synthesized compounds might act as Topo II catalytic inhibitors. Certain compounds displayed potent Topo II inhibition at 10 μM. The cytotoxic activities of these compounds against HeLa, A549, Raji, PC-3, MDA-MB-201, and HL-60 cancer cell lines were evaluated. The results indicated that these compounds exhibited strong antiproliferative activity. A good relationship was observed between the Topo II inhibitory potency and the cytotoxicity of these compounds. The structure–activity relationship revealed that the electronic effects, the phenyl group, and the rhodanine moiety were particularly important for the Topo II inhibitory potency and cytotoxicity.

The piperazine ring is a very important factor in governing molecular structure to generate the special properties of a compound. New NBD-based fluorescent probes 1–3 were designed and synthesized for hydrogen sulfide (H2S) detection. Probe 1 showed high sensitivity and selectivity for H2S with a color change from yellow to pink for naked eye observation. However, the analogues (2 and 3) were response-negative toward H2S. In order to clarify the importance of the piperazine ring in the NBD-based H2S probe and the mechanism, the crystal structure of 1 was obtained and the piperazine ring was deemed to mediate H2S nucleophilic addition. In addition, probe 1 had limits of detection of 18.96 μM (UV) and 23.42 μM (FL), and the thiolysis rate for 1 was found to be 0.49 M−1 s−1. Living cell imaging results indicated that probe 1 could be utilized to trace intracellular H2S. This work has a great guiding role in the design of NBD-based fluorescent probes through a nucleophilic addition mechanism.

Curcuma longa L. rhizomes collected from 20 different habitats in China are used to analyze yield, composition and bioactivity of essential oils extracted from them. The yield of the 20 essential oils vary from 4.03 to 5.27% depending on the habitat where they were collected. Using gas chromatography–mass spectrometry (GC–MS), 81 components are identified in the 20 essential oils, and their major compounds are ar-turmerone (0.92–42.85%), β-turmerone (5.13–42.54%), α-zingiberene (0.25–25.05%), ar-curcumene (1.21–15.70%) and β-sesquiphellandrene (0.05–14.88%). The essential oils of rhizomes collected from different habitats exhibit different antimicrobial activities, and the essential oils from Guangxi have generally better activities. These essential oils also show different DPPH (IC50, 4.37–11.59 μg/mL) and ABTS (IC50, 4.21–13.25 μg/mL) radical-scavenging activities, being most of them more effective than Trolox C (IC50, 10.72 and 11.42 μg/mL). They also exhibit significantly different cytotoxicity against B16 cells (IC50, 13.96–135.97 μg/mL) and LNCaP cell (IC50, 19.63–127.81 μg/mL), and essential oils from Luchuan in Guangxi have the highest cytotoxicity. Some essential oils show outstanding anti-inflammatory activities by markedly down-regulating the expression of inflammatory cytokines, cyclooxygenase 2 (COX-2) and tumor necrosis factor (TNF)-α, in vivo. Therefore, Curcuma longa L. rhizome, one of the popular traditional Chinese medicines with excellent bioactivities, can be more rationally utilized based on their chemical composition and bioactivity in the further.

International audience; The presence of amyloid plaques predisposes clinical symptoms of cognitive impairment, which occurs much earlier than other clinical symptoms and plays a crucial role in the neuropathology of AD. Thus, developing probes for Aβ species imaging could be used for early diagnosis of AD, and blocking the initial steps of Aβ aggregation with small molecules has emerged as a valid disease-modifying therapy for Aβ. Herein, we report the design, synthesis and evaluation of a series of new theranostic agents, which can simultaneously perform near infra-red imaging of Aβ plaques, prevent self-aggregation of Aβ monomer, disaggregate preformed Aβ fibrils and play a protective effect on the toxicity of human neuroblastoma cells (SHSY5Y) induced by Aβ1–42. Most of these probes displayed maximum emission in PBS (>650 nm), which falls in the good range for NIRF probes. Importantly, these probes are found to have a high binding affinity toward Aβ aggregates, to exhibit a large fluorescence enhancement upon interaction with Aβ aggregates accompanied by a blueshift in the emission spectra of 20–40 nm and to show an excellent targeting ability for Aβ plaques in slices of brain and eye containing retina tissue from double transgenic mice. These molecules show a promising potential as theranostic agents for the diagnosis and therapy of AD.

The Vernohia anthelmintica L.’s extract is one of the most popular Uygur medicines used for vitiligo. It is believed that the chalcone compounds of the plant play an important role in the treatment since they may activate tyrosinase and improve melanin production. In this study, twenty-one chalcones and nine analogues were synthesized in view of three different components of chalcone (A, B ring and α, β-unsaturated carbonyl). After biological evaluation of their activity on tyrosinase in cell-free systems, the result showed that most compounds (except polyhydroxy chalcones) possess activator effect on the tyrosinase, especially for 13a–15a, 20a and 1b, which bearing a comparable activity to the positive control 8-MOP. SAR of these tyrosinase activator was summed up for the first time as well. Finally, compound 13a was found to increase melanin contents and tyrosinase activity 1.75 and 1.3 fold, respectively, compared with that of untreated murine B16 cells at the concentration of 40 μg/mL.

Early detection of Alzheimer’s disease (AD) is imperative in enabling the understanding and clinical treatment of this disorder, as well as in preventing its progression. Imaging agents specifically targeting Aβ plaques in the brain and the retina may lead to the early diagnosis of AD. Among them, near-infrared fluorescent (NIRF) imaging has emerged as an attractive tool to noninvasively identify and monitor diseases during the preclinical and early stages. In the present study, we report the design, synthesis, and evaluation of a series of new near-infrared fluorescent probes. Most of these probes displayed maximum emission in PBS (>650 nm), which falls in the good range for NIRF probes. Among them, 4a1 showed the highest affinity toward Aβ aggregates (Kd = 7.5 nM) and an excellent targeting ability for Aβ plaques in slices of brain and retina tissue from double transgenic mice. These compounds are also found to effectively prevent Aβ fibril formation and disaggregate preformed Aβ fibrils, showing a prom...

International audience; A global burden of Alzheimer's disease (AD) has been growing over last decades. Evidence indicates that β-amyloid (Aβ) production and senile plaque deposition in the brain is causative in the onset of AD pathogenesis. It appears much earlier than cognitive decline and plays a key role in initiating and developing AD neuropathology. As such, there is an intense passion with discovering theranostic agents which make a significant impact in diagnostic and therapy. Herein, we report an investigation of novel phenothiazine-based compounds as promising potential theranostic agents for AD. Remarkably, they have exhibited a high binding affinity toward Aβ aggregates, a good biostability and a strong increase in their fluorescence intensity with blue shift when interacting with Aβ aggregates. Furthermore, they have been simultaneously applied to perform NIR in vivo imaging of β-amyloid plaques in double transgenic AD mouse model, to prevent self-aggregation of Aβ monomer from forming toxic oligmers and to reduce Aβ-induced toxicity of human neuroblastoma cells (SH-SY5Y).

International audience; Brain amyloid deposits have been identified as the main neuropathological hallmarks of Alzheimer's diseases (AD) and intensive efforts have been devoted to develop aggregation inhibitors preventing the formation of toxic oligomeric Aβ for therapeutic. In addition, evidence indicates that the formation and accumulation of β−amyloid plaques probably precede clinical symptoms by around 20 years and imaging of such plaques would be beneficial for early-stage AD detection. In this study, we investigated phenothiazine-based compounds as novel promising theranostic agents for AD. These multifunctional agents exhibited BBB permeability, low neurotoxicity, good bio-stability as well as strong turn-on fluorescence with a Stokes shift upon binding to Aβ aggregates. They had metal-chelating property which could delay Aβ aggregation and displayed high binding affinity for β−amyloid aggregates. Moreover, they have been simultaneously applied to perform in vivo near-infrared fluorescence imaging of β-amyloid plaques in double transgenic AD mouse model, to prevent self-aggregation of Aβ monomer from forming toxic oligomers and to protect human neuroblastoma SH-SY5Y cells against Aβ-induced toxicity and oxidative stress.

International audience; An efficient and practical procedure was developed to prepare various N-pyrimidin[1,3,4]oxadiazole and thiadiazole scaffolds using a Buchwald-type coupling. The products of this reaction are otherwise difficult to access and could be used as building blocks in drug design.

Background The content of collagen and elastin occupies a large proportion of skin evaluation, and collagen peptide (CP) and elastin peptide (EP) are widely used drugs, which have anti-inflammatory effects. In addition, CP and EP can also be used as therapeutic agents for skin repair. However, previous studies have never thoroughly verified the effects of oral administration of CP and EP on skin repair. Aim To study the effects and mechanism of oral administration of CP and EP on skin aging induced by combinatorial treatment with D-galactose and ultraviolet radiation. Results In animal experiments, the combined oral administration of CP and EP increased the contents of collagen and elastin in animal skin, accompanying with significantly upregulated expression of hyaluronic acid and hydroxyproline, as well as significantly reduced expression of MMP-3 and IL-1α. In addition, the combined therapy also significantly increased the expression of seven collagen and elastin synthesis-related factors including IGF-1, LOX, SMAD2, JNK, SP1, TβRII and TGF-β. Conclusion Oral administration of CP and EP can repair skin aging induced by the combined treatment with D-galactose and ultraviolet radiation and the effects of CP and EP appeared synergistic.

NiO nanoparticles deposited on FTO glass modified surface were used to adsorb an organic dye. The obtained device was covered with PEDOT/PSS polymers blend and later sprinkled with palladium nanoparticles. This modified hybrid electrode was used under ligth and than under dark conditions to study the reduction reaction of CO2 in solution. The results obtained indicated a large shift toward positive potential of the reduction wave of CO2 in solution under light when compared to the same reduction wave under dark in the same conditions. The obtained results will be presented and discussed in the frame of the state of the art of CO2 reduction catalysed by palladium nanoparticles supported by hybrid charge transport material.

In order to develop original water soluble antagonists of X‐linked inhibitor of apoptosis protein (XIAP), a novel bicyclic scaffold was designed based on 8,5‐fused bicyclic lactam. During its preparation, a spontaneous rearrangement from 8,5‐ to 7,5‐fused bicyclic lactam was observed and confirmed by MS and NMR analyses, in particular the HMBC spectra. DFT calculations were performed to understand the corresponding mechanism. It was finally prevented through changing the reaction order in the synthesis route and a Smac mimetic with this core structure, ZJ‐1 was successfully obtained. The structure of this new bicyclic scaffold was well confirmed by HRMS and NMR (1H, 13C, NOESY) analyses. ZJ‐1 presented in addition a binding affinity to XIAP‐BIR3, nearly 6 times better than that of AVPI, similar to the reported SM‐128 in an in vitro fluorescence polarization (FP) assay. This preliminary result suggests that this new bicyclic scaffold could be very attractive in the development of novel anticancer agents targeting XIAP.

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In this paper, we investigate the effect of glabridin (Glab) on psoriasis. We observed that Glab significantly suppressed the levels of nitric oxide (NO), NF-κB subunit p65, interleukin (IL)-6, and IL-1β in lipopolysaccharide (LPS)-stimulated HaCaT cells. In addition, Glab treatment reduced the expression of IL-17A, IL-22, and IL-23 in TNF-α-stimulated-HaCaT cells. These findings prompted us to test whether Glab could be used to treat psoriasis in vivo. The effects of Glab on PASI scores, histopathological changes, oxidative/anti-oxidative indexes and pro-inflammatory cytokines in IMQ-induced mice were investigated. The results indicated that Glab could reduce the PASI scores and ameliorate the deteriorating histopathology. Interestingly, RT-PCR revealed that Glab significantly decreased the mRNA expression of p65, IL-6, IL-1β, IL-17A, IL-22, and IL-23. These results were confirmed by Western blot analysis and immunohistochemistry staining. In conclusion, our present study revealed that Glab had beneficial effects on psoriasis, and the underlying mechanism may be associated with the downregulation of pro-inflammatory cytokines and the improvement of antioxidant status. Hence, Glab is a promising candidate molecule for development of effective psoriasis therapies.

In this paper, an efficient colorimetric and fluorescent probe based on a benzothiadiazole derivative was developed for the detection of fluoride ions (F−). The selectivity of this approach capitalized on the highly selective and straightforward chemical reaction between F− and the Si–O bond. The sensing behavior of this probe towards anions was monitored by UV-visible and fluorescence spectroscopies in acetonitrile–aqueous buffer mixtures. Among the tested anions: F−, Cl−, Br−, I−, ClO4−, NO3−, CN−, HSO4−, AcO− and H2PO4− only F− induced a remarkable red-shift (149 nm) in the absorption spectrum which is concomitant with a color change from colorless to pink. This probe provides a new approach for naked-eyed detection of F− and the detection limit was calculated to be 1.7 μM. Besides, a concomitant fluorescence decrease was also observed. These results demonstrated that the probe could detect F− with excellent sensitivity and selectivity in complicated samples.

Novel topoisomerase II (Topo II) inhibitors have gained considerable interest for the development of anticancer agents. In this study, a series of carbazole derivatives containing chalcone analogs (CDCAs) were synthesized and investigated for their Topo II inhibition and cytotoxic activities. The results from Topo II mediated DNA relaxation assay showed that CDCAs could significantly inhibit the activity of Topo II, and the structure-activity relationship indicated the halogen substituent in phenyl ring play an important role in the activity. Further mechanism studies revealed that CDCAs function as non-intercalative Topo II catalytic inhibitors. Moreover, some CDCAs showed micromolar cytotoxic activities. The most potent compound 3h exhibited notable growth inhibition against four human cancer cell lines. Flow cytometric analysis revealed that compounds 3d and 3h arrested the HL-60 cells in sub G1 phase by induction of apoptosis. It was further confirmed by Annexin-V-FITC binding assay. Western blot analysis revealed that compound 3h induces apoptosis likely through the activation of caspase proteins.

In this work, we report a reagentless electrochemical peptide (AVPFAQKG) sensor to directly detect the BIR3 domain of X-linked inhibitor of apoptosis protein (XIAP-BIR3). The bioreceptor was based on a conducting copolymer film electrosynthesized from juglone and a juglone-peptide conjugate (JP) newly designed. The peptide–protein interactions generated an important increase of steric hindrance at the interface and a current decrease (signal off) of the redox reaction from quinone embedded in the polymer backbone as evidenced by Square Wave Voltammetry. This allowed a specific and sensitive detection of XIAP-BIR3 with a detection limit of 1 nM (13 ng mL −1 ). The peptide–protein complex could be then dissociated by adding the free precursor peptide (AVPFAQKG) into solution, causing a shift-back on the signal, i.e. an increase in the current intensity (signal-on). This “off–on” detection sequence was used in this work as a double verification of the specificity and this approach can be employed as a general way to increase the reliability of the results. In general, the approach described in this work may be inspired to develop other direct and reagentless electrochemical protein assays with high specificity and sensitivity.

(5S,8S,10aR)-tert-butyl 5-(tert-butoxycarbonylamino)-2,6-dioxooctahydro-1H-pyrrolo[2,1-d][1,5]oxazocine-8-carboxylate 5, containing an original proline-like moiety, was prepared through Yamaguchi lactonization. However, it was observed that this 8 + 5 bicyclic lactone was spontaneously rearranged to the corresponding 7 + 5 bicyclic lactam under acid conditions, used to remove the Boc/tBu protecting groups. Both core structures were confirmed by one-dimensional and two-dimensional NMR, as well as HRMS. The new proline-like moieties are unknown up to now, and the 7 + 5 bicyclic lactam, much more stable than its precursor, may represent a valuable template to develop constrained non-peptide mimetics.

Psoriasis is a chronic inflammatory and immune-mediated skin disease. Although certain agents have shown clinical success in treating psoriasis, development of safe and effective strategies for the treatment of this condition remains important. Research suggests that DNA topoisomerase I (Topo I) inhibitors may have potent psoriasis-ameliorating effects. Here, 25 quinoline derivatives were synthesized and identified as Topo I inhibitors. These compounds inhibited the 12-O-tetradecanoylphorbol-13-acetate-induced mouse ear inflammation. The most potent analogs, 5i and 5l, suppressed the expression of inflammatory cytokines in lipopolysaccharide-stimulated HaCaT cells. Additionally, the lead compounds significantly improved imiquimod-induced psoriasis-like inflammation in mice. Moreover, the expression levels of cytokines and inflammatory mediators, such as interleukin (IL)-17A, IL-22, IL-23, nuclear factor-κB subunit p65, tumor necrosis factor-α, and interferon-γ, were dramatically inhibited in the dorsal skin of 5i- and 5l-treated mice. These findings indicate that the inhibition of Topo I activity may potentially be an effective strategy for psoriasis treatment.

Multi-component inorganic-organic hybrids are tunable units used to build-up mesoscopic architectures / devices for various applications. We focus our interest on hybrid materials for the elaboration of photoelectrodes to be integrated into solar-energy conversion devices, such as solid-state Dye-sensitized Solar Cells (ss-DSCs, for photovoltaic conversion) and Dye-sensitized PhotoElectrosynthesis Cells (DSPECs, for photocatalytic conversion to “Solar Fuels”). In order to improve charge transfers and transport within photoelectrodes, along with overall stability and efficiency, we use controlled-deposition electrochemical techniques (for example, in situ electro-assisted PhotoElectroPolymerization (PEP)) for the preparation of the Hole-Transporting Material (HTM, used as a charge carrier within the device) on the photosensitized mesoporous semi-conductor of the electrode. This allows a better filling of mesoporous materials and a better contact between the components of the hybrid material/electrode.[i] We also remove the physical interface between components (for example, between Dye/HTM) by introducing a covalent bond between components (molecular engineering of bifunctional conjugates).[ii] We will present our recent progress on NiO-based p-type photocathodes for low-temperature CO2 reduction, based on electrocatalytic and photoelectrochemical approaches. [i] Zhang, J. et al. Nano Energy, 2016, 19, 455-470. [ii] A. Delices et al. Electrochim. Acta, 2018, 269, 163-171. Figure 1

International audience; Barbituric acid derivatives are prochiral molecules, i.e. they are chiral upon adsorption on surfaces. Scanning tunneling microscopy reveals that barbituric acid derivatives self-assemble into a chiral guest-host supramolecular architecture at the solid-liquid interface on graphite. The host nanoarchitecture has a sophisticated wavy shape pattern and paired guest molecules are nested insides the cavities of the host structure. Each unit cell of the host structure is composed of both enantiomers with a ratio of 1:1. Furthermore, the wavy patterns of the nanoarchitecture are formed from alternative appearance of left- and right-handed chiral building blocks, which makes the network heterochiral. The functional guest-host nanoarchitecture is the result of two-dimensional chiral amplification from single enantiomers to organizational heterochiral supramolecular self-assembly.