Anion-Controlled Assembly of a Silver-Responsive Bifunctional Coordination Polymer with Detection and Large Adsorption Capacity.

The recognition and adsorption of silver ions (Ag+) from industrial wastewater are necessary but still challenging. Herein, we constructed four Zn(II)-based coordination polymers (CPs), namely, [Zn(btap)2(NO3)2]n (1), [Zn(btap)(SO4)(H2O)3]n (2), {[Zn(btap)2(H2O)2]·(ClO4)2}n (3), and [Zn(btap)Cl2]n (4), by using 3,5-bis(triazol-1-yl)pyridine (btap) with different anionic Zn(II) salts. The crystal structures of 1-4, varying from one-dimensional beaded (1) and zigzag chain (2) to two-dimensional sql (3) and bex (4) typologies, were regulated by the coordination modes of btap and the counter-anions. The water stability, pH stability, thermostability, and luminescent properties of the CPs were investigated. The luminescence performances in a series of cations and anions were also explored. Considering the high density of chloride groups in the structure, 4 showed luminescence sensing for Ag+ [KSV = 9188.45 M-1 and a limit of detection (LOD) of 4.9 µM], as well as an excellent ability for Ag+ adsorption in aqueous solution (maximum adsorption capacity, 653.3 mg/g). Additionally, anti-interference experiments revealed that 4 had excellent recognition and adsorption capacities for Ag+ even when multiple ions coexisted. Moreover, XRD, EDS, and XPS analyses confirmed that the coordination of Ag+ with chloride groups in 4 resulted in excellent adsorption capacity and prevented ligand-to-ligand electron transfer, showing excellent detection ability. Suitable coordination sites were introduced to interact strongly with Ag+, along with detection and large adsorption capacity. Our strategy can effectively design and develop multifunctional CP-based materials, which are applicable in removal processes and environmental protection, by regulating anions in the self-assembly and introducing CP functional groups.

A novel Schiff base cobalt(III) complex induces a synergistic effect on cervical cancer cells by arresting early apoptosis stage.

A new schiff base cobalt(III) complex [N,N'-bis(2'-hydroxyphenylacetone)-o-ethanediamine] cobalt(III) (M3) has been synthesized and characterized by single X-ray crystallography. The cytotoxicity of complex M3 was evaluated against HeLa, LoVo, A549, A549/cis cancer cell lines, and the normal cell lines LO2 by MTT assays. The IC50 is in the range of 6.27-22.68 µM, which is somewhat lower than cisplatin on the basis of platinum molar concentration. Furthermore, anticancer mechanistic studies showed that the complex M3 inhibited cell proliferation by blocking DNA synthesis and then acted on nuclear division of HeLa cells over time. Moreover, western blot analysis indicated M3 dramatically decreased the target protein c-Myc and KLF5 expression levels, and activated many signaling pathways including ER stress, apoptosis, cell cycle and DNA damage in HeLa. M3 did not affect proteasomal activity.

Discovery of arylamide-5-anilinoquinazoline-8-nitro derivatives as VEGFR-2 kinase inhibitors: Synthesis, in vitro biological evaluation and molecular docking.

Herein, we embarked on a structural optimization campaign aiming at the discovery of novel anticancer agents with our previously reported XL-6f as a lead compound. A library of 23 compounds has been synthesized based on the highly conserved active site of VEGFR-2. Several title compounds exhibited selective inhibitory activities against VEGFR-2, which also displayed selective anti-proliferation potency against HepG2 cell. All synthesized compounds were evaluated for anti-angiogenesis capability. Compound 7o showed the most potent anti-angiogenesis ability, the efficient cytotoxic activities (in vitro against HUVEC and HepG2 cell lines with IC50 values of 0.58 and 0.23 µM, respectively). The molecular docking analysis revealed 7o is a Type-II inhibitor of VEGFR-2 kinase. In general, these results indicated these arylamide-5-anilinoquinazoline-8-nitro derivatives are promising inhibitors of VEGFR-2 for the potential treatment of anti-angiogenesis.

Isopentyl-Sulfide-Impregnated Nano-MnO2 for the Selective Sorption of Pd(II) from the Leaching Liquor of Ores.

Conventional separation methods are not suitable for recovering palladium present in low concentrations in ore leaching solutions. In this study, a novel isopentyl sulfide (S201)-impregnated α-MnO2 nanorod adsorbent (BISIN) was prepared, characterized, and applied for the selective adsorption and separation of palladium from the leaching liquor of ores. Batch studies were carried out, and the main adsorption parameters were systematically investigated, in addition to the relevant thermodynamic parameters, isotherms, and kinetic models. The thermodynamic parameters reflected the endothermic and spontaneous nature of the adsorption. Moreover, the experimental results indicated that the Langmuir isotherm model fits the palladium adsorption data well and the adsorption was well described by the pseudo-second-order kinetic model. The main adsorption mechanisms of palladium were elucidated at the molecular level by X-ray crystal structure analysis. Thiourea was found to be an excellent desorption agent, and the palladium-thiourea complex was also confirmed by X-ray crystal structure analysis. The results indicated that almost all of the Pd(II) (>99.0%) is adsorbed on BISIN, whereas less than 2% of the adsorbed Pt(IV), Fe3+, Cu2+, Ni2+, and Co2+ is observed under the optimum conditions. The proposed method can be used for the efficient adsorption and separation of palladium from the leaching liquor of ores.

The antigluconeogenic activity of cucurbitacins from Momordica charantia.

Five new cucurbitacins, kuguacins II-VI (1-5), along with five known analogues (6-10), were obtained from the fruit of Momordica charantia. Structures of the new compounds were elucidated as 5ß,19-epoxycucurbit-23-en-7-on-3ß,25-diol (1), 5ß,19-epoxycucurbit-7,23-dion-3ß,25-diol (2), 5ß,19-epoxycucurbit-6-en-19,23-dion-3ß,25-diol (3), 5ß,19-epoxy-23,24,25,26,27-pentanorcucurbit-6-en-7,19-dion-3ß,22-diol (4), and cucurbit-5-en-7,23-dion-3ß,19,25-triol (5) by extensive spectroscopic and single-crystal X-ray diffraction analyses. Some cucurbitane compounds from this species were screened for their potential antidiabetic properties in terms of antigluconeogenic activity. As a result, compounds 1, 10, 11, and 12 (at 25-100 µM) showed concentration-dependent inhibition on glucose production from liver cells. In addition, compounds 11 and 12 (at 100 µM) showed around 20-30 % inhibition on PEPCK activity.

(8-Hydroxyquinoline) Gallium(III) Complex with High Antineoplastic Efficacy for Treating Colon Cancer via Multiple Mechanisms.

A series of (8-hydroxyquinoline) gallium(III) complexes (CP-1-4) was synthesized and characterized by single X-ray crystallography and density functional theory (DFT) calculation. The cytotoxicity of the four gallium complexes toward a human nonsmall cell lung cancer cell line (A549), human colon cancer cell line (HCT116), and human normal hepatocyte cell line (LO2) was evaluated using MTT assays. CP-4 exhibited excellent cytotoxicity against HCT116 cancer cells (IC50 = 1.2 ± 0.3 µM) and lower toxicity than cisplatin and oxaliplatin. We also evaluated the anticancer mechanism studies in cell uptake, reactive oxygen species analysis, cell cycle, wound-healing, and Western blotting assays. The results showed that CP-4 affected the expression of DNA-related proteins, which led to the apoptosis of cancer cells. Moreover, molecular docking tests of CP-4 were performed to predict other binding sites and to confirm its higher binding force to disulfide isomerase (PDI) proteins. The emissive properties of CP-4 suggest that this complex can be used for colon cancer diagnosis and treatment, as well as in vivo imaging. These results also provide a foundation for the development of gallium complexes as potent anticancer agents.

Multifunctional O-phenanthroline silver(I) complexes for antitumor activity against colorectal adenocarcinoma cells and antimicrobial properties by multiple mechanisms.

A series of O-phenanthroline silver(I) complexes were synthesized and characterized by infrared (IR) spectroscopy, mass spectrometry (MS), 1H nuclear magnetic resonance (NMR) spectroscopy and single-crystal X-ray crystallography. The cytotoxicity of the silver(I) complex (P-131) was evaluated in the cancer cell lines HCT-116, HeLa, and MDA-MB-231 and the normal cell line LO2 via MTT assays. The 50% inhibition concentration (IC50) of P-131 on HCT116 cell line is 0.86 ± 0.03 µM. It is far lower than the IC50 value of cisplatin (9.08 ± 1.10 µM), the IC50 value of normal cell LO2 (76.20 ± 0.48 µM) is much higher than that of cisplatin (3.99 ± 0.74 µM), indicating that its anticancer effect is stronger than that of cisplatin, and its biological safety is greater than that of cisplatin. Furthermore, anticancer mechanistic studies showed that P-131 inhibited cell proliferation by blocking DNA synthesis and acted temporally on the nucleus in dividing HCT-116 cells. Moreover, P-131 increased intracellular reactive oxygen species (ROS) levels in a dose-dependent manner. Notably, 10 mg/kg P-131 showed better antitumor effects than oxaliplatin in an HCT116 human colorectal xenograft mouse model without inducing toxicity. Moreover, the microdilution broth method was used to evaluate the antimicrobial properties of P-131 against Pseudomonas aeruginosa and Candida albicans. A biofilm eradication study was also performed using the crystal violet method and confocal laser scanning microscopy.

Gallium Metal-Organic Nanoparticles with Albumin-Stabilized and Loaded Graphene for Enhanced Delivery to HCT116 Cells.

Background: Gallium (III) metal-organic complexes have been shown to have the ability to inhibit tumor growth, but the poor water solubility of many of the complexes precludes further application. The use of materials with high biocompatibility as drug delivery carriers for metal-organic complexes to enhance the bioavailability of the drug is a feasible approach. Methods: Here, we modified the ligands of gallium 8-hydroxyquinolinate complex with good clinical anticancer activity by replacing the 8-hydroxyquinoline ligands with 5-bromo-8-hydroxyquinoline (HBrQ), and the resulting Ga(III) + HBrQ complex had poor water solubility. Two biocompatible materials, bovine serum albumin (BSA) and graphene oxide (GO), were used to synthesize the corresponding Ga(III) + HBrQ complex nanoparticles (NPs) BSA/Ga/HBrQ NPs and GO/Ga/HBrQ NPs in different ways to enhance the drug delivery of the metal complex. Results: Both of BSA/Ga/HBrQ NPs and GO/Ga/HBrQ NPs can maintain stable existence in different solution states. In vitro cytotoxicity test showed that two nanomedicines had excellent anti-proliferation effect on HCT116 cells, which shown higher level of intracellular ROS and apoptosis ratio than that of cisplatin and oxaliplatin. In addition, the superior emissive properties of BSA/Ga/HBrQ NPs and GO/Ga/HBrQ NPs allow their use for in vivo imaging showing highly effective therapy in HCT116 tumor-bearing mouse models. Conclusion: The use of biocompatible materials for the preparation of NPs against poorly biocompatible metal-organic complexes to construct drug delivery systems is a promising strategy that can further improve drug delivery and therapeutic efficacy.

A novel water-soluble heptaplatin analogue with improved antitumor activity and reduced toxicity.

A novel water-soluble heptaplatin analogue, cis-[(4R,5R)-4,5-bis-(aminomethyl)-2-isopropyl-1,3-dioxolane](3-hydroxy-1,1-cyclobutanedicarboxylato)platinum(II), has been synthesized and biologically evaluated. The complex shows more activity and less toxicity than its parent drug heptaplatin, exhibiting the great potential for further development.

Triaqua-1κO-µ-cyanido-1:2κN:C-penta-cyanido-2κC-tetra-kis-(dimethyl-formamide-1κO)-1-holmium(III)-2-iron(III) monohydrate.

In the bimetallic cyanide-bridged title complex, [Fe(0.98)HoRu(0.02)(CN)(6)(C(3)H(7)NO)(4)(H(2)O)(3)]·H(2)O, the Ho(III) ion is in a slightly distorted square-anti-prismatic arrangement formed by seven O atoms from four dimethyl-formamide (DMF) mol-ecules and three water mol-ecules, and one N atom from a bridging cyanide group connected with the Fe(III) atom which is octa-hedrally coordinated by six cyanide groups. In the crystal, mol-ecules are held together through O-H⋯N and O-H⋯O hydrogen-bonding inter-actions to form a three-dimensional framework. Elemental analysis of one of the precursors and the crystal shows that there is a slight contamination of Fe by Ru. The Fe site displays, therefore, small substitutional disorder with site-occupancy factors Fe/Ru = 0.98:0.02. The two methyl groups of two dimethyl-formamide ligands are positionally disordered with site-occupancy factors of 0.44 (3):0.56 (3) and 0.44 (3):0.56 (3).

Anion-controlled Zn(II) coordination polymers with 1-(tetrazo-5-yl)-3-(triazo-1-yl) benzene as an assembling ligand: synthesis, characterization, and efficient detection of tryptophan in water.

Tryptophan regulates and participates in various physiological systems in the human body, and its excessive intake has harmful effects. Therefore, detecting and monitoring tryptophan in water and distinguishing it from other amino acids are necessary. In addition to their excellent luminescence, coordination polymer-based sensors have good stability and high sensitivity and selectivity for sensing applications. In this work, two luminescent coordination polymers (CPs), [Zn(ttb)Cl]n (1) and [Zn2(ttb)2(OH)(NO3)]n (2), were obtained through the solvothermal reaction of different Zn(II) salts with a rarely studied multidentate N-donor ligand, 1-(tetrazo-5-yl)-3-(triazo-1-yl) benzene (Httb). Crystallographic investigations revealed that the structure of 1 exhibits a 2D fes net with Cl- anions acting as terminal charge balancers, and that of 2 features a 3D ant net with NO3- anions in a rare monodentate bridging (µ2-O-η1:η1) mode. In terms of stability tests, 2 has better thermal and water stability than 1. Although both show good fluorescence performance, specific tryptophan detection, and excellent anti-interference ability, 2 has higher KSV (111 852.6 M-1), a lower limit of detection (LOD = 23.6 nM), and a better recovery rate than 1. Cytotoxicity experiments proved that 2 has extremely low toxicity and thus has great potential for in vivo detection. Therefore, CP 2 is a suitable candidate for advanced practical applications for the efficient sensing of tryptophan in water. The luminescence of the ligands was also calculated using DFT theory and further discussed through experiments. The quenching mechanism that occurs after tryptophan addition was explored through Hirshfeld surface analysis.

Unusual dimeric chemical structure for a carboplatin analogue as a potential anticancer complex.

An unexpected and unusual dimeric platinum(II) tetracarboxylate complex was obtained by the reaction of cis-[Pt(NH(3))(2)I(2)] with disilver dicarboxylate. The complex exhibits greater in vitro anticancer activity and lower toxicity in mice than its parent compound, carboplatin, and is therefore worthy of further evaluation as a potential antitumor dinuclear platinum agent.

Henrylactones A-E and anti-HBV constituents from Illicium henryi.

Five new sesquiterpene lactones, henrylactones A-E ( 1- 5), together with ten known compounds: cycloparvifloralone ( 6), tashironin ( 7), tashironin A ( 8), neoanisatin ( 9), anisatin ( 10), anislactone B ( 11), 7- O-acetylanislactone B ( 12), merrillianolide ( 13), cyclomerrillianolide ( 14) and pseudomajucin ( 15), were isolated from the stems and roots of ILLICIUM HENRYI. Their structures were elucidated based on extensive spectroscopic data analyses. Among them, henrylactone A ( 1) is a novel sesquiterpene with a dilactone moiety and its structure was confirmed by X-ray diffraction. Sesquiterpene lactones 1- 15 were tested for their anti-hepatitis B virus (HBV) activities. The most active compound, tashironin ( 7), exhibited an IC (50) value of 0.48 mM (SI = 6.3) inhibiting on HBV surface antigen (HBsAg) secretion and an IC (50) value of 0.15 mM (SI = 20.1) inhibiting on HBV e antigen (HBeAg) secretion using HBV transfected Hep G2.2.15 cell line.

A new Schiff base copper(II) complex induces cancer cell growth inhibition and apoptosis by multiple mechanisms.

A new Schiff base copper(II) complex [N,N'-bis(2'-hydroxyphenylacetone)-o-ethanediamine] copper (II) (M1) has been synthesized and characterized by single X-ray crystallography. The cytotoxicity of complex M1 was evaluated against HeLa, LoVo, A549, A549/cis cancer cell lines, and the normal cell lines LO2 and HUVEC, by MTT (3-(4,5-dimethylthiazoyl-2-yl)2,5-diphenyltetrazoliumbromide) assays. The IC50 (50% inhibition concentrations) is in the range of 5.13-11.68 µM, which is somewhat lower than cisplatin on the basis of platinum molar concentration. Furthermore, anticancer mechanistic studies showed that the complex M1 inhibited cell proliferation by blocking DNA synthesis and then acted on nuclear division of HeLa cells over time. Moreover, M1 increased intracellular ROS (Reactive oxygen species) levels in a dose-dependent manner. Western blot analysis indicated M1 dramatically decrease c-Myc transcription factor and KLF5 (Krüppel-like factor 5) protein expression levels in HeLa. M1 did not inhibit proteasomal activity. Finally, M1 induced DNA damages and activated the DNA damage repair pathways.

A novel aryltetralone lignan from Litsea pedunculata.

A novel aryltetralone lignan, pedunculine A (1), together with a known lignan cagayanone A (2), was isolated from the leaves and twigs of Litsea pedunculata. The structure of the new lignan was elucidated on the basis of spectroscopic methods and single-crystal X-ray diffraction.

Tris[2-(2-pyridylimino-meth-yl)phenol-ato(0.67-)]europium(III) nitrate.

The title compound, [Eu(C(12)H(9.33)N(2)O)(3)]NO(3), was obtained by the reaction of Eu(NO(3))·3H(2)O and the Schiff base ligand 2-(2-pyridylimino-meth-yl)phenol. The Eu atom is located on a threefold rotation axis and is nine-coordinated by three tridentate Schiff base ligands in a distorted tricapped trigonal-prismatic geometry. The O atom at the phenol hydr-oxy group is partially deprotonated and the H atoms are modelled with one-third occupancy according to the space group R. Offset face-to-face π-π [centroid-centroid distance = 3.886 (3) Å] and edge-to-face C-H⋯π inter-actions are found between adjacent mol-ecules. An intra-molecular O-H⋯N hydrogen bond is also present.

Bis(acetyl-acetonato-κO,O')-aqua-(diacetyl-methanido-κC)iridium(III).

In the crystal structure of the title compound, [Ir(C(5)H(7)O(2))(3)(H(2)O)], the Ir(III) atom is six-coordinated and situated in a slightly distorted octa-hedral environment. The complex contains both Ir-O and Ir-C bonds and was isolated from a reaction mixture of IrCl(3)(H(2)O)(x), pentane-2,5-dione and NaHCO(3). O-H⋯O hydrogen bonding between the water molecules and the carbonyl O atoms of adjacent molecules leads to a layered motif extending parallel to (010).

Design, synthesis and in vitro evaluation of 6-amide-2-aryl benzoxazole/benzimidazole derivatives against tumor cells by inhibiting VEGFR-2 kinase.

Herein, we have carried out a structural optimization campaign to discover the novel anti-tumor agents with our previously screened YQY-26 as the hit compound. A library of thirty-seven 6-amide-2-aryl benzoxazole/benzimidazole derivatives has been designed and synthesized based on the highly conserved active site of VEGFR-2. Several title compounds exhibited selective inhibitory activities against VEGFR-2 than EGFR kinases, which also displayed selective anti-proliferation potency against the HUVEC and HepG2 than the A549 and MDA-MB-231 cancer cell lines. The newly synthesized compounds were evaluated for anti-angiogenesis capability by chick chorioallantoic membrane (CAM) assay. Among them, compounds 9d showed the most potent anti-angiogenesis ability (79% inhibition at 10 nM/eggs), the efficient cytotoxic activities (in vitro against the HUVEC and HepG2 cell lines with IC50 values of 1.47 and 2.57 µM, respectively), and excellent VEGFR-2 kinase inhibition (IC50 = 0.051 µM). The molecular docking analysis revealed that compound 9d is a Type II inhibitor of VEGFR-2 kinase. These results indicated that the 6-amide-2-arylbenzoxazole and 6-amide-2-aryl benzimidazole derivatives are promising inhibitors of VEGFR-2 kinase for the potential treatment of anti-angiogenesis.

Discovery of 6-Arylurea-2-arylbenzoxazole and 6-Arylurea-2-arylbenzimidazole Derivatives as Angiogenesis Inhibitors: Design, Synthesis and in†vitro Biological Evaluation.

We embarked on a structural optimization campaign aimed at the discovery of novel anti-angiogenesis agents with previously reported imidazole kinase inhibitors as a lead compound. A library of 29 compounds was synthesized. Several title compounds exhibited selective inhibitory activities against vascular endothelial growth factor receptor 2 (VEGFR-2) over epidermal growth factor receptor (EGFR) kinase; these compounds also displayed selective and potent antiproliferative activity against three cancer cell lines. The newly synthesized compounds were evaluated for anti-angiogenesis activity by chick chorioallantoic membrane (CAM) assay. Among them, 1-(2-(2-chlorophenyl)benzo[d]oxazol-5-yl)-3-(4-(trifluoromethoxy)phenyl)urea (compound 5 n) showed the most potent anti-angiogenesis capacity, efficient cytotoxic activities (in vitro against human umbilical vein endothelial cells (HUVEC), H1975, A549, and HeLa cell lines, with respective IC50 values of 8.46, 1.40, 7.61, and 0.28 µm), and an acceptable level of VEGFR-2 kinase inhibition (IC50 =0.25 µm). Molecular docking analysis revealed 5 n to be a type II inhibitor of VEGFR-2 kinase. In general, these results indicate that these 6-arylurea-2-arylbenzoxazole/benzimidazole derivatives are promising inhibitors of VEGFR-2 kinase for potential development into anti-angiogenesis drugs.

The antilipolytic action of bis(alpha-furancarboxylato)oxovanadium(IV) in adipocytes.

BACKGROUND: Previously, bis(alpha-furancarboxylato)oxovanadium(IV)(BFOV) exhibited potent hypoglycemic activity in diabetic animals. We evaluated the effects of BFOV on lipolysis in isolated rat adipocytes and lipid metabolism in fat-fed/streptozotocin (STZ)-induced diabetic rats, an animal model of type 2 diabetes. METHODS: Antilipolytic action of BFOV was investigated by observing free fatty acids (FFA) release in isolated rat adipocytes treated with epinephrine and forskolin. Diabetic rats were induced by high-fat feeding plus STZ injection (25 mg/kg, i.p.). The rats were randomly divided into non-diabetic, diabetic, diabetic-BFOV (0.02, 0.06 and 0.2 mmol/kg) and diabetic-vanadyl sulfate group. All substances were given intragastrically to rats for 4 weeks. The concentrations of blood glucose, serum lipid and leptin, as well as body weight and food intake were determined. RESULTS: FFA release from adipocytes treated with epinephrine was markedly inhibited by BFOV and vanadyl sulfate, with the IC(50) values of 0.30+/-0.20 and 0.46+/-0.26 mmol/l, respectively, but not by insulin. Whereas, the inhibition of vanadyl compounds on FFA release triggered by forskolin in adipocytes were not observed. BFOV dose-dependently reduced serum triglycerides and FFA concentrations when compared with untreated diabetic rats (P<0.05), while it did not influence cholesterol concentrations, similar to vanadyl sulfate. Serum leptin concentration was also decreased both in the BFOV- and vanadyl sulfate-treated diabetic group (P<0.05). Moreover, BFOV markedly reduced blood glucose concentration and food intake (P<0.05), but it did not change the body weight of diabetic rats. CONCLUSION: BFOV has an antilipolytic action in adipocytes mediated by catecholamines. This action was distinct from that of insulin and also not related to inhibiting the activity of adenylate cyclase. In vivo, BFOV could improve dyslipidemia and leptin sensitivity in fat-fed/STZ-diabetic rats.