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Abstract: A new sensor (LWZn) based on 7-diethylaminocoumarin Schiff base was synthesized to detect Zn2+ in the red emission region due to its extended π-conjugation structure and the strong electron-withdrawing capability of nitrile groups. Although LWZn alone has weak fluorescence, its fluorescence intensity shows a 35-fold increase after combining with Zn2+ probably due to the inhibition of the conformational change in the excited state upon complexation with Zn2+. In addition, LWZn shows a good selectivity to Zn2+ over other metal cations, especially Cd2+, which often responds together with Zn2+. [Copyright &y& Elsevier]

Abstract: In this work, we have successfully prepared a series of new sterol-based cationic lipids (1–4) via an efficient ‘Click’ chemistry approach. The pDNA binding affinity of these lipids was examined by EB displacement and agarose-gel retardant assay. The average particle sizes and surface charges of the sterol-based cationic lipids/pDNA lipoplexes were analyzed by dynamic laser light scattering instrument (DLS), and the morphologies of the lipoplexes were observed by atomic force microscopy (AFM). The cytotoxicity of the lipids were examined by MTT and LDH assay, and the gene transfection efficiencies of these lipid carriers were investigated by luciferase gene transfection assay in various cell lines. In addition, the intracellular uptake and trafficking/localization behavior of the Cy3-DNA loaded lipoplexes were preliminarily studied by fluorescence microscopy. The results demonstrated that the pDNA loading capacity, lipoplex particle size, zeta potential and morphology of the sterol lipids/pDNA lipoplexes depended largely on the molecular structure factors including sterol-skeletons and headgroups. Furthermore, the sterol-based lipids showed quite different cytotoxicity and gene transfection efficacy in A549 and HeLa cells. Interestingly, it was found that the cholesterol-bearing lipids 1 and 2 showed 7–104 times higher transfection capability than their lithocholate-bearing counterparts 3 and 4 in A549 and HeLa cell lines, suggested that the gene transfection capacity strongly relied on the structure of sterol skeletons. Moreover, the study on the structure–activity relationships of these sterol-based cationic lipid gene carriers provided a possible approach for developing low cytotoxic and high efficient lipid gene carriers by selecting suitable sterol hydrophobes and cationic headgroups. [Copyright &y& Elsevier]

Abstract: A new coumarin-derived imine IC1 was designed for highly selective sensing of Zn2+ over Cd2+ ions in aqueous solution based on a controllable Czation mechanism. Methyl as a fine controllable unit was incorporated into IC1 to tune the conformational change of imine and thus significantly improve its selectivity to Zn2+ compared with methyl-free imine IC2. Sensor IC1 was also utilized to image intracellular Zn2+ ions in HepG2 cells with a good performance. [Copyright &y& Elsevier]

Abstract: Stimuli-responsive biomaterials derived from natural products toward efficient drug/gene delivery have been attracting increasing attention in the past decade. In this work, we first designed and prepared a new series of cholesterol-disulfide lipids, namely CHOSS-N, CHOSS-N+, CHOSS-Lys and CHOSS-4N bearing cholesterol and a variety of headgroups via disulfide and carbonate bond linkages, and their molecular structures were characterized by NMR and ESI-MS. Furthermore, plasmid DNA binding affinity for these new CHOSS lipids was separately examined by ethidium bromide displacement and agarose-gel retardant assay. Average diameter sizes and surface potentials of the CHOSS/pDNA lipoplex particles prepared under various N/P charge ratios were analyzed by dynamic laser light scattering (DLS). Under 10 mm dithiothreitol (DTT), stability and disassembly of the CHOSS/pDNA lipoplex nanoparticles were investigated by agarose-gel retardant assay and atomic force microscopy (AFM). Employing a COS-7 cell line, cell viability was examined for the prepared CHOSS lipids and their pDNA lipoplexes with branched PEI-25k as the reference. Finally, COS-7 cell gene transfection efficacies with these CHOSS lipids as potential delivery vectors were investigated by luciferase and EGFP transfection assay in the absence and presence of serum, and intracellular uptake capability, trafficking and cellular localization of Cy3-labeled pEGFP-N1 DNA were studied with a flow cytometer and fluorescent microscopy with Lipofectamine™ 2000 as the control. The results demonstrated low cytotoxicity, strong pDNA binding affinity and high transgenetic efficacy for new prepared CHOSS lipids, and particularly high intracellular uptake capability and specific cellular localization of pDNA at the periphery of cell nuclei were for the first time interestingly observed for the CHOSS lipid delivery carriers. In general, these may pave a new way to utilize cholesterol, amino acids and other functional natural products to prepare efficient gene/drug delivery carriers with simple structure and low cytotoxicity. [Copyright &y& Elsevier]

Abstract: A coumarin azine derivative: 3,3′-hydrazine-1,2-diylidenebis(methan-1-yl-1-ylidene)bis(7-(diethyl amino)-2H-chromen-2-one) (ligand 1) was synthesized and characterized. It was used as a colorimetric chemosensor for Hg2+. The absorption maximum of ligand 1 shows a large red shift from 490nm to 565nm (Δ =75nm) in the presence of Hg2+. The change in color is very easily observed by the naked eye, while other metal cations, such as Fe2+, Co2+, Ni2+, Zn2+, Cd2+, Cu2+, Fe3+, Ag+, Pb2+, alkali metal and alkaline earth metal cations do not induce such a change. [Copyright &y& Elsevier]

Abstract: In this work, we first synthesized a ω-amino group Boc-protected poly(ω-aminohexyl methacrylamide) PAHMAA-Boc precursor via controlled reversible addition-fragmentation chain transfer (RAFT) polymerization of the Boc-AHMAA monomer in THF solution, and poly(ω-aminohexyl methacrylamide) (PAHMAA) was then prepared via Boc deprotection, and was further conjugated with (l-)-arginines at the ω-amino group sites to give a series of new (l-)-arginine conjugated PAHMAA-R7, PAHMAA-R16 and PAHMAA-R22. Employing these PAHMAA and PAHMAA-Rs as functional gene vectors, their plasmid DNA binding affinities were examined by agarose gel retardant assay. By means of dynamic light scattering (DLS), mean particle sizes and zeta potentials of the polyplexes were analyzed. Moreover, cytotoxicities of the PAHMAA and PAHMAA-Rs were evaluated by MTT and lactate dehydrogenase (LDH) release assays with COS-7 cells, and luciferase and EGFP gene transfection efficacies by these vectors were assayed in COS-7 and HeLa cells. Furthermore, intracellular uptake of the vector/Cy3-labeled pDNA polyplexes was studied with a flow cytometer (FACS), and the most efficient PAHMAA-R16 vector was employed to investigate the endocytic gateways with various inhibitors. In addition, colocalization of the Cy3-labeled pDNA and Oregon Green labeled PAHMAA-R16 vector in the intracellular organelles of COS-7 cells was visualized on a fluorescence microscopy. As a result, it was revealed that the PAHMAA-R vectors showed lower cytotoxicities and transfection efficacies significantly higher than those of the PAHMAA, strongly depending on their percentage of arginine conjugation, and that the results of endocytic inhabitation and fluorescence colocalization in endoplasmic reticulum may suggest a caveolae-mediated efficient intracellular trafficking route for the synthesized PAHMAA-R vectors. [Copyright &y& Elsevier]

Abstract: A rhodamine spirolactam/2-hydrazinopyridine derivative was synthesized and characterized, which exhibited high selectivity to Cu2+ over other metal cations. The Cu2+ recognition of this rhodamine derivative could be detected by fluorescence spectra, absorption spectra and an obvious color change which was observed easily by naked-eyes. The binding of this rhodamine derivative to Cu2+ is instantaneous and sensitive. Moreover, a linear relationship was found between the fluorescence intensity at 575nm from 0.5×10−6 M to 3.0×10−6 M of Cu2+ concentration, and the limit of detection (LOD) was at low concentration of 2.11×10−8 M, this would benefit for the establishment of standard working curves in practical Cu2+detection. Additionally, we synthesized rhodamine spirolactam/2-aminomethylpyridine derivative and rhodamine spirolactam/phenylhydrazine derivative as analogs for elucidate the structure-recognition relationships. Finally, we prepared the test strips of rhodamine spirolactam/2-hydrazinopyridine derivative for practical chromogenic the Cu2+ detection. [Copyright &y& Elsevier]

α -Santonin, a sesquiterpene lactone isolated from Artemisia Santonica , possesses diverse bioactivities including antioxidant, anti-inflammation, immunosuppressive, anti-roundworm, anti-malaria, etc. However, its bioactivities are not satisfactory and need to be further optimized. Thus, many α -santonin derivatives were synthesized on the basis of rings A, B and C for the discovery of new analogues with prominent bioactivities. Herein, we reviewed and discussed the related synthetic methodologies, diverse bioactivities and structure-activity relationships (SAR) of α -santonin derivatives. Image 1 • We summarized numerous synthetic strategies of α -santonin derivatives on the basis of rings A, B and C in α -santonin. • Various bioactivities of α -santonin derivatives were reviewed comprehensively. • The SAR study of diverse bioactivities with different targets was described in detail. [ABSTRACT FROM AUTHOR]

Phosgene and mustard gas are highly toxic chemicals that severely threaten public security and human health. To ensure public security, monitoring these chemical warfare agents (CWAs) is necessary. Many fluorescent probes have been developed for detecting CWAs because of their high sensitivity, facile manipulation, and visual signal output. In this review, we introduced the recent progress of various fluorescent probes for phosgene and mustard gas detection, including recognition sites, sensing mechanisms, and structure-function relationships. Furthermore, the challenges and perspectives of fluorescent probes for CWAs were briefly stated. We hope this review will provide constructive information to develop the most advanced fluorescent probes towards CWAs. • This review sums the state-of-the-art about fluorescent probes for phosgene and SM. • This review gives specific attention to reaction mechanisms of fluorescent probes. • This review introducts the fundamental principles and strategies for creating probes. • This review points out the trends for development of fluorescent probes for CWAs. • This review proposes the future outlook of fluorescent probes for CWAs. [ABSTRACT FROM AUTHOR]

Demethylzeylasteral (DEM), a class of terpenoids isolated from natural plants, frequently exhibits moderate or limited inhibitory effect on tumor growth across multiple cancer types. Thus, here we attempted to elevate the anti-tumor efficacy of DEM by altering active groups in its chemical structure. Initially, we synthesized a series of novel DEM derivatives 1 – 21 through performing a series of modifications of its phenolic hydroxyl groups at C-2/3, C-4 and C-29 positions. The anti-proliferative activities of these new compounds were subsequently assessed using three human cancer cell line models (A549, HCT116 and HeLa) and CCK-8 assay. Our data showed that compared to original DEM compound, derivative 7 exhibited remarkable inhibition effect on A549 (16.73 ± 1.07 μM), HCT116 (16.26 ± 1.94 μM) and HeLa (17.07 ± 1.09 μM), almost reaching to the same level of DOX. Moreover, the structure-activity relationships (SARs) of the synthesized DEM derivatives were discussed in detail. We found that treatment with derivative 7 only led to moderate cell cycle arrest at S-phase in a concentration-dependent manner. Meanwhile, derivative 7 treatment markedly induced apoptosis in tumor cells. Consistent with this observation, our subsequent docking analysis showed that derivative 7 is capable of activating caspase-3 through interaction with the His 121 and Gly 122 residues of the enzyme. Overall, we have developed a new series of DEM derivatives with elevated anti-tumor efficacy relative to its parent form. The results suggested that derivative 7 has great potential to be employed as an anticancer agent candidate for natural product-based cancer chemotherapy. [Display omitted] [ABSTRACT FROM AUTHOR]

A family of anthracene carboxyimides with multi-color fluorescence have been successfully prepared, and their spectroscopic properties were investigated by UV–vis absorption spectroscopy, steady-state and time-resolved fluorescence spectroscopy. The photostability and solvatochromic fluorescence in organic solvents were also investigated. The parent anthracene carboxyimide 4a displays very strong green fluorescence (Φ F = 0.91 in EtOH), good pH stability and photostability, as well as a large Stokes shift. By attachment of different substituents at the 10-position of the anthracene carboxyimide, the fluorescence maxima could be effectively modulated from 500 nm to 615 nm. The 10-(picolylamine) substituted anthracene carboxyimides 5a and 5b exhibit large Stokes shifts (>80 nm) and significant positive solvatochromic fluorescence in organic solvents due to their intramolecular charge-transfer (ICT) character. Furthermore, cell staining experiments indicate that anthracene carboxyimides have excellent cell membrane permeability and good photo-bleaching resistance in living cells. Particularly, compound 5a is a specific mitochondria-targeting dye with red fluorescence. All these features enable anthracene carboxyimides to serve as promising candidates for bio-labeling/imaging applications. [ABSTRACT FROM AUTHOR]

[Display omitted] Protein tyrosine phosphatase (PTP1B) antagonizes insulin signaling and acts as a potential therapeutic target for insulin resistance associated with obesity and type II diabetes. In this work, a series of isosteviol derivatives 1–28 was synthesized and the inhibitory activity on PTP1B was evaluated by double antibody sandwich ELISA (DAS-ELISA) in vitro. Most isosteviol derivatives showed moderate PTP1B inhibitory activities. Among them, derivatives 10 , 13 , 24 , 27 showed remarkable bioactivities with IC 50 values ranging from 0.24 to 0.40 µM. Particularly, derivative 24 exhibited the best inhibitory activity against PTP1B (IC 50 = 0.24 µM) in vitro ; moreover, it showed 7-fold selectivity to PTP1B over T -cell protein tyrosine phosphatase (TCPTP) and 14-fold selectivity to PTP1B over cell division cycle 25 homolog B (CDC25B). Molecular docking studies demonstrated the hydrogen bond interaction between 24 and LYS-116 residue in PTP1B might be essential for the inhibitory activity. The results suggested that derivative 24 has great potential to be employed as drug candidate for the treatment of obesity and type II diabetes. [ABSTRACT FROM AUTHOR]

Pentacyclic triterpenoids are important natural products widely presenting in nature with rich bioactivities. Tripterygium wilfordii Hook. f., a precious Chinese medicinal material, is used to cure rheumatoid arthritis, nephrotic syndrome, systemic lupus erythematosus. Triterpenoids are one of the important active components of Tripterygium wilfordii Hook. f. Demethylzeylasteral extracted from Tripterygium wilfordii Hook. f. had numerous pharmacological effects, including anticancer, anti-inflammatory, immune suppression, anti-fertility, antivirus, antimicrobial. In this paper, we summarized comprehensively pharmacological activities of demethylzeylasteral for potential application as a therapeutic agent. [Display omitted] [ABSTRACT FROM AUTHOR]

Formaldehyde (FA) and phosgene are toxic volatile organic compounds (TVOCs) that pose serious threats to environment and human health. Herein, we rationally designed a fluorescent sensing platform Nap-NH2 for the detection of FA and phosgene in different emission channels. Upon an aldimine condensation reaction with FA, Nap-NH2 exhibited a significant fluorescence "turn-on" response at 551 nm with high selectivity and a low detection limit (62 nM). In contrast, Nap-NH2 underwent a specific nucleophilic reaction with phosgene, triggering a fluorescence band at 487 nm with fast response and a low detection limit (23 nM). The sensor was fabricated into cheap and portable test strips, which showed differentiable fluorescence colors and response rates to determine FA and phosgene. A smartphone containing RGB color detector was used to record the fluorescence pictures of test strips in the presence of FA or phosgene, and quantitatively determine the levels of FA and phosgene. Furthermore, Nap-NH2 test strips coupled with 5G mobile smartphone realized remote online monitoring gaseous phosgene and FA. Therefore, this 5G smartphone-adaptable fluorescence sensing platform has great potential applications in environment and public security. [Display omitted] • A fluorescent sensing platform for the differentiated detection of formaldehyde and phosgene. • The probe generate different fluorescence color to indicate formaldehyde and phosgene. • The probe showed high sensitivity and selectivity toward formaldehyde and phosgene with low limits of detection. • A smartphone-adaptable test kits for the monitoring of gaseous phosgene and formaldehyde. [ABSTRACT FROM AUTHOR]

Abstract: Development of highly efficient nonviral gene delivery vectors still remains a great challenge. In this study, we report a new gene delivery vector based on dendrimer-entrapped gold nanoparticles (Au DENPs) with significantly higher gene transfection efficiency than that of dendrimers without AuNPs entrapped. Amine-terminated generation 5 poly(amidoamine) (PAMAM) dendrimers (G5.NH2) were utilized as templates to synthesize AuNPs with different Au atom/dendrimer molar ratios (25:1, 50:1, 75:1, and 100:1, respectively). The formed Au DENPs were used to complex two different pDNAs encoding luciferase (Luc) and enhanced green fluorescent protein (EGFP), respectively for gene transfection studies. The Au DENPs/pDNA polyplexes with different N/P ratios and compositions of Au DENPs were characterized by gel retardation assay, light scattering, zeta potential measurements, and atomic force microscopic imaging. We show that the Au DENPs can effectively compact the pDNA, allowing for highly efficient gene transfection into the selected cell lines as demonstrated by both Luc assay and fluorescence microscopic imaging of the EGFP expression. The transfection efficiency of Au DENPs with Au atom/dendrimer molar ratio of 25:1 was at least 100 times higher than that of G5.NH2 dendrimers without AuNPs entrapped at the N/P ratio of 2.5:1. The higher gene transfection efficiency of Au DENPs is primarily due to the fact that the entrapment of AuNPs helps preserve the 3-dimensional spherical morphology of dendrimers, allowing for more efficient interaction between dendrimers and DNA. With the less cytotoxicity than that of G5.NH2 dendrimers demonstrated by thiazoyl blue tetrazolium bromide assay and higher gene transfection efficiency, it is expected that Au DENPs may be used as a new gene delivery vector for highly efficient transfection of different genes for various biomedical applications. [Copyright &y& Elsevier]

• A glycodendron/Ppa-functionalized HA was prepared for tumor photodynamic therapy. • Dendronized HA showed high tumor accumulation and excellent anticancer effect. • The therapeutic indexes of HA-based nanomedicines are enhanced via glycodendron. To enhance the drug delivery efficiency of hyaluronic acid (HA), we designed and prepared glycodendron and pyropheophorbide-a (Ppa)-functionalized HA (HA-Ppa-Dendron) as a nanosystem for cancer photodynamic therapy. Linear Ppa-modified HA (HA-Ppa) was also prepared as a control. Cellular uptake of both polymers by MDA-MB-231 cells led to mitochondrial dysfunction and generation of reactive oxygen species under the irradiation of a laser. Compared to the linear polymer, HA-Ppa-Dendron had higher molecular weight, a more compact nanoscale particle size, and a dendritic structure, resulting in a much longer blood circulation time and higher tumor accumulation. HA-Ppa-Dendron outperformed HA-Ppa in inhibiting cell growth, with 60 % of tumors was eradicated under laser irradiation. Tumor growth inhibition (TGI) up to 99.2 % was achieved from HA-Ppa-Dendron, which was much higher than that of HA-Ppa (50.6 %). Therefore, glycodendron-functionalized HAs by integration of HA and dendritic polymers may act as efficient anti-cancer nanomedicine. [ABSTRACT FROM AUTHOR]