Developing Benign Ni/g-C3N4 Catalysts for CO2 Hydrogenation: Activity and Toxicity Study.

This research discusses the CO2 valorization via hydrogenation over the non-noble metal clusters of Ni and Cu supported on graphitic carbon nitride (g-C3N4). The Ni and Cu catalysts were characterized by conventional techniques including XRD, AFM, ATR, Raman imaging, and TPR and were tested via the hydrogenation of CO2 at 1 bar. The transition-metal-based catalyst designed with atom-economy principles presents stable activity and good conversions for the studied processes. At 1 bar, the rise in operating temperature during CO2 hydrogenation increases the CO2 conversion and the selectivity for CO and decreases the selectivity for methanol on Cu/CN catalysts. For the Ni/CN catalyst, the selectivity to light hydrocarbons, such as CH4, also increased with rising temperature. At 623 K, the conversion attained ca. 20%, with CH4 being the primary product of the reaction (CH4 yield >80%). Above 700 K, the Ni/CN activity increases, reaching almost equilibrium values, although the Ni loading in Ni/CN is lower by more than 90% compared to the reference NiREF catalyst. The presented data offer a better understanding of the effect of the transition metals' small metal cluster and their coordination and stabilization within g-C3N4, contributing to the rational hybrid catalyst design with a less-toxic impact on the environment and health. Bare g-C3N4 is shown as a good support candidate for atom-economy-designed catalysts for hydrogenation application. In addition, cytotoxicity to the keratinocyte human HaCaT cell line revealed that low concentrations of catalysts particles (to 6.25 µg mL-1) did not cause degenerative changes.

A small molecule inhibitor of PCSK9 that antagonizes LDL receptor binding via interaction with a cryptic PCSK9 binding groove.

Proprotein convertase (PC) subtilisin kexin type 9 (PCSK9) inhibits the clearance of low density lipoprotein (LDL) cholesterol from plasma by directly interacting with the LDL receptor (LDLR). As the interaction promotes elevated plasma LDL cholesterol levels and a predisposition to cardiovascular disease (CVD), it has attracted much interest as a therapeutic target. While anti-PCSK9 monoclonal antibodies have been successful in the treatment of hypercholesteremia by decreasing CVD risk, their high cost and a requirement for injection have prohibited widespread use. The advent of an orally bioavailable small molecule inhibitor of the PCSK9-LDLR interaction is an attractive alternative, however efforts have been tempered as the binding interface is unfavourable for binding by small organic molecules. Despite its challenging nature, we report herein the discovery of compound 3f as a small molecule inhibitor of PCSK9. The kinase inhibitor nilotinib emerged from a computational screen that was applied to identify compounds that may bind to a cryptic groove within PCSK9 and proximal to the LDLR-binding interface. A subsequent in vitro PCSK9-LDLR binding assay established that nilotinib was a bona fide but modest inhibitor of the interaction (IC50 = 9.8 µM). Through multiple rounds of medicinal chemistry, 3f emerged as a lead-like molecule by demonstrating disruption of the PCSK9-LDLR interaction at nanomolar levels in vitro (IC50 = 537 nM) with no inhibitory activity (IC50 > 10 µM) against a small panel of kinases. Compound 3f restored LDL uptake by liver cells at sub-micromolar levels and demonstrated excellent bioavailability when delivered subcutaneously in mice. Most significantly, compound 3f lowered total cholesterol levels in the plasma of wild-type mice, thereby providing proof-of-concept that the notion of a small molecule inhibitor against PCSK9 is therapeutically viable.

Synthesis of flower-like magnetite nanoassembly: Application in the efficient reduction of nitroarenes.

A facile approach for the synthesis of magnetite microspheres with flower-like morphology is reported that proceeds via the reduction of iron(III) oxide under a hydrogen atmosphere. The ensuing magnetic catalyst is well characterized by XRD, FE-SEM, TEM, N2 adsorption-desorption isotherm, and Mössbauer spectroscopy and explored for a simple yet efficient transfer hydrogenation reduction of a variety of nitroarenes to respective anilines in good to excellent yields (up to 98%) employing hydrazine hydrate. The catalyst could be easily separated at the end of a reaction using an external magnet and can be recycled up to 10 times without any loss in catalytic activity.

Hexagonal Mesoporous Silica-Supported Copper Oxide (CuO/HMS) Catalyst: Synthesis of Primary Amides from Aldehydes in Aqueous Medium.

Hexagonal mesoporous silica (HMS)-supported copper oxides (CuO/HMS) have been prepared by a sol-gel method and characterized by X-ray diffraction, FTIR spectroscopy, transmission electron microscopy, N2 sorption, inductively coupled plasma (ICP), X-ray photoelectron spectroscopy (XPS), H2 temperature-programed reduction (TPR), NH3 temperature-programed desorption (TPD), and high-resolution (HR)-TEM techniques. An analysis of these results revealed a mesoporous material system with a high surface area (974 m2 g-1 ) and uniform pore-size distribution. The catalytic efficacy of CuO on the HMS support with varying Cu loadings (1, 3, 5, 10, and 15 wt %) was investigated for the transformation of aldehydes to primary amides; 3 wt % CuO/HMS exhibited good catalytic performance with good to excellent yields of amides (60-92 %) in benign aqueous medium. The intrinsically heterogeneous catalyst could be recovered after the reaction and reused without any noticeable loss in activity.

In Situ Generation of Pd-Pt Core-Shell Nanoparticles on Reduced Graphene Oxide (Pd@Pt/rGO) Using Microwaves: Applications in Dehalogenation Reactions and Reduction of Olefins.

Core-shell nanocatalysts are a distinctive class of nanomaterials with varied potential applications in view of their unique structure, composition-dependent physicochemical properties, and promising synergism among the individual components. A one-pot microwave (MW)-assisted approach is described to prepare the reduced graphene oxide (rGO)-supported Pd-Pt core-shell nanoparticles, (Pd@Pt/rGO); spherical core-shell nanomaterials (∼95 nm) with Pd core (∼80 nm) and 15 nm Pt shell were nicely distributed on the rGO matrix in view of the choice of reductant and reaction conditions. The well-characterized composite nanomaterials, endowed with synergism among its components and rGO support, served as catalysts in aromatic dehalogenation reactions and for the reduction of olefins with high yield (>98%), excellent selectivity (>98%) and recyclability (up to 5 times); both Pt/rGO and Pd/rGO and even their physical mixtures showed considerably lower conversions (20 and 57%) in dehalogenation of 3-bromoaniline. Similarly, in the reduction of styrene to ethylbenzene, Pd@Pt core-shell nanoparticles (without rGO support) possess considerably lower conversion (60%) compared to Pd@Pt/rGO. The mechanism of dehalogenation reactions with Pd@Pt/rGO catalyst is discussed with the explicit premise that rGO matrix facilitates the adsorption of the reducing agent, thus enhancing its local concentration and expediting the hydrazine decomposition rate. The versatility of the catalyst has been validated via diverse substrate scope for both reduction and dehalogenation reactions.

Kinase Inhibitor Indole Derivatives as Anticancer Agents: A Patent Review.

Cancer accounts for a number of deaths each year. Consequently, prevention of this deadly disease is more challenging and hence the invention of new anticancer agents is of utmost importance. The current review elaborates the importance of indole designs as patented in the form of anticancer druglike molecules targeting different cites of biological arena. Specific attention was given to kinases such as platelet-derived growth factor receptor, vascular endothelial growth factor receptor and fibroblast growth factor receptor, Bruton's tyrosine kinase, anaplastic lymphoma kinase, Janus kinase, cyclin-dependent kinase aurora kinases A, B and C, checkpoint kinases, protein kinase R, Pim kinases, phosphoinositide 3- kinase, altered proteins kinases, polo-like kinase and many more. Moreover, the article summarizes the mode of action through the particular functions of kinases and the inhibitory potential of indole derivatives toward specific kinase. Certain patents gathered in the existing review article suggest that indole core can be a versatile foundation to discover drug-like kinase inhibitor molecules and modification of substituents existing on the indole moiety may have important impact on the pharmacokinetic and pharmacodynamics aspects of the resultant scaffolds. The information presented here would gather a great deal of interest to identify the new molecular designs bearing indole nucleus presenting novel anticancer drugs with a wide variety of biological targets involved in cancer pathology focusing on the inhibition of tyrosine kinases, serine/threonine-specific protein kinases, cyclin-dependent kinases, lipid kinases and altered protein kinases.

Piperazine derivatives for therapeutic use: a patent review (2010-present).

INTRODUCTION: Piperazine, a six membered nitrogen containing heterocycle, is of great significance to the rational design of drugs. This moiety can be found in a plethora of well-known drugs with various therapeutic uses, such as antipsychotic, antihistamine, antianginal, antidepressant, anticancer, antiviral, cardio protectors, anti-inflammatory, and imaging agents. Slight modification to the substitution pattern on the piperazine nucleus facilitates a recognizable difference in the medicinal potential of the resultant molecules. AREAS COVERED: Scifinder was the main source used to search for patents containing piperazine compounds with therapeutic uses. The article describes a variety of molecular designs bearing piperazine entity furnishing CNS agents, anticancer, cardio-protective agents, antiviral, anti-tuberculosis, anti-inflammatory, antidiabetic, and antihistamine profiles, as well as agents relieving pain and useful in imaging applications. EXPERT OPINION: The great interest gathered to explore piperazine based molecules in relatively few years reflects the broad potential of the entity. Earlier, this scaffold was considered to express CNS activity only. However, a significant increase in research covering studies of several different activities of piperazine ring suggest a successful emergence of the pharmacophore. Certain patents outlined in the present article recommend that piperazines can be a flexible building block to discover drug-like elements and modification of substituents present on the piperazine ring may have a significant impact on the pharmacokinetic and pharmacodynamics factors of the resulting molecules. This article aims to provide insights to piperazine based molecular fragments that would assist drug discoverers to rationally design molecules for various diseases. We anticipate, and highly recommend, further therapeutic investigations on this motif.

Chrysin-piperazine conjugates as antioxidant and anticancer agents.

Synthesis of 7-(4-bromobutoxy)-5-hydroxy-2-phenyl-4H-chromen-4-one intermediate treating chrysin with 1,4-dibromobutane facilitated combination of chrysin with a wide range of piperazine moieties which were equipped via reacting the corresponding amines with bis(2-chloroethyl)amine hydrochloride in diethylene glycol monomethyl ether solvent. Free radical scavenging potential of prepared products was analyzed in vitro adopting DPPH and ABTS bioassay in addition to the evaluation of in vitro anticancer efficacies against cervical cancer cell lines (HeLa and CaSki) and an ovarian cancer cell line SK-OV-3 using SRB assay. Bearable toxicity of 7a-w was examined employing Madin-Darby canine kidney (MDCK) cell line. In addition, cytotoxic nature of the presented compounds was inspected utilizing Human bone marrow derived mesenchymal stem cells (hBM-MSCs). Overall, 7a-w indicated remarkable antioxidant power in scavenging DPPH(·) and ABTS(·+), particularly analogs 7f, 7j, 7k, 7l, 7n, 7q, 7v, 7w have shown promising free radical scavenging activity. Analogs 7j and 7o are identified to be highly active candidates against HeLa and CaSki cell lines, whereas 7h and 7l along with 7j proved to be very sensitive towards ovarian cancer cell line SKOV-3. None of the newly prepared scaffolds showed cytotoxic nature toward hBM-MSCs cells. From the structure-activity point of view, nature and position of the electron withdrawing and electron donating functional groups on the piperazine core may contribute to the anticipated antioxidant and anticancer action. Different spectroscopic techniques (FT-IR, (1)H NMR, (13)C NMR, Mass) and elemental analysis (CHN) were utilized to confirm the desired structure of final compounds.

Regio- and chemoselective reduction of nitroarenes and carbonyl compounds over recyclable magnetic ferrite-nickel nanoparticles (Fe(3)O(4)-Ni) by using glycerol as a hydrogen source.

Reduction by magnetic nano-Fe(3)O(4)-Ni: a facile, simple and environmentally friendly hydrogen-transfer reaction that takes place over recyclable ferrite-nickel magnetic nanoparticles (Fe(3)O(4)-Ni) by using glycerol as hydrogen source allows aromatic amines and alcohols to be synthesized from the precursor nitroarenes and carbonyl compounds.