Diphenylurea Research Articles

Diphenyl urea-benzylidene acetohydrazide hybrids as fibroblast growth factor receptor1 inhibitors and anticancer agents.

Molecular hybridization between diphenyl urea and benzylidene acetohydrazide was adopted for the design of a new series of FGFR-1 targeting cancer. The designed series was synthesized and submitted to NCI-USA to be screened for their growth inhibitory activity on NCI cancer cell lines. Some of the synthesized hybrids displayed promising growth inhibitory activity on NCI cancer cell lines with a mean GI% between 70.39% and a lethal effect. Compounds 9a, 9i, 9j, and 9n-p were further selected for a five-dose assay and all the tested candidates showed promising antiproliferative activity with GI50 reaching the submicromolar range. Encouraged by the potent activity of 9a on colon cancer on the one hand and the well-known overexpression of FGFR-1 in it on the other hand, it was further selected as a representative example to be evaluated for its mechanism on the cell cycle and apoptosis of HCT116 cell line. Interestingly, 9a was found to pause the cell cycle of the HCT116 cell line at the G1 phase and induced late apoptosis. In parallel, all the synthesized hybrids 9a-p were examined for their potential to inhibit FGFR-1 at 10 µM. Compounds 9a, 9g, 9h, and 9p were found to have potent inhibitory activity with % inhibition = 63.04%, 58.31%, 60.87% and 79.84%, respectively. Molecular docking simulation of 9a in the binding pocket of FGFR-1 confirms its capability to achieve the characteristic interactions of the type II FGFR-1 inhibitors. Exploration of the ADME properties of 9a-p by SwissADME web tool proved their satisfactory physicochemical properties for the discovery of new anticancer hits.

Synthesis, in vitro, and in silico study of novel pyridine based 1,3-diphenylurea derivatives as tyrosinase inhibitors

Tyrosinase inhibitors are studied in the cosmetics and pharmaceutical sectors as tyrosinase enzyme is involved in the biosynthesis and regulation of melanin, hence these inhibitors are beneficial for the management of melanogenesis and hyperpigmentation-related disorders. In the current work, a novel series of diphenyl urea derivatives containing a halo-pyridine moiety (5a–t) was synthesized via a multi-step synthesis. In vitro, tyrosinase inhibitory assay results showed that, except for two compounds, the derivatives were excellent inhibitors of human tyrosinase. The average IC50 value of the inhibitors (15.78 μM) is lower than that of kojic acid (17.3 μM) used as the reference compound, indicating that, on average, these molecules are more potent than the reference. Derivative 5a was identified as the most potent human tyrosinase inhibitor of the series, with an IC50 value of 3.5 ± 1.2 μM, approximately 5 times more potent than kojic acid. To get further insights into the nature of binding site interactions, molecular docking and molecular dynamics simulation studies were carried out. Moreover, the evaluation of in silico ADME properties showed a highly favorable profile for the synthesized compounds. These findings suggested that the further development of this class of compounds could be useful to get potent drug-like compounds that can target hyperpigmentation-related disorders.

Expanding the π-system of Fatty Acid-Anion Transporter Conjugates Modulates Their Mechanism of Proton Transport and Mitochondrial Uncoupling Activity.

Mitochondrial uncoupling by small molecule protonophores is a promising strategy for developing novel anticancer agents. Recently, aryl urea substituted fatty acids (aryl ureas) were identified as a new class of protonophoric anticancer agents. To mediate proton transport these molecules self-assemble into membrane-permeable anionic dimers in which intermolecular hydrogen bonds between the carboxylate and aryl-urea anion receptor delocalise the negative charge across the aromatic π-system. In this work, we extend the aromatic π-system by introducing a second phenyl substituent to the aryl urea scaffold and compare the proton transport mechanisms and mitochondrial uncoupling actions of these compounds to their monoaryl analogues. It was found that incorporation of meta-linked phenyl substituents into the aryl urea scaffold enhanced proton transport in vesicles and demonstrated superior capacity to depolarise mitochondria, inhibit ATP production and reduce the viability of MDA-MB-231 breast cancer cells. In contrast, diphenyl ureas linked through a 1,4-distribution across the phenyl ring displayed diminished proton transport activity, despite both diphenyl urea isomers possessing similar binding affinities for carboxylates. Mechanistic studies suggest that inclusion of a second aryl ring changes the proton transport mechanism, presumably due to steric factors that impose higher energy penalties for dimer formation.

Anion Binding Interaction Enhances the Robustness of Iodide for High-Performance Perovskite Solar Cells.

Owing to the ionic bond nature of the Pb-I bond, the iodide at the interface of perovskite polycrystalline films was easily lost during the preparation process, resulting in the formation of a large number of iodine vacancy defects. The presence of iodine vacancy defects can cause nonradiative recombination, provide a pathway for iodide migration, and be harmful to the power conversion efficiency (PCE) and stability of organic-inorganic hybrid perovskite solar cells (HPSCs). Here, in order to increase the robustness of iodides at the interface, a strategy to introduce anion binding effects was developed to stabilize the perovskite films. It was demonstrated that the N,N'-diphenylurea (DPU), characterized by high anionic binding constants and a Y-shaped structure, provides a relatively strong hydrogen bond donor site to effectively reduce the iodine loss during film preparation and inhibits iodide migration in the device working condition. As expected, the reduced iodine loss considerably improves the quality of the perovskite films and suppresses nonradiative recombination. The performance of the device after DPU modification was significantly increased, with the PCE rising from 23.65 to 25.01% with huge stability enhancement as well.

Chemical profiling of bioactive compounds in the methanolic extract of wild leaf and callus of Vitex negundo using gas chromatography-mass spectrometry.

The investigation of plant-based therapeutic agents in medicinal plants has revealed their presence in the extracts and provides the vision to formulate novel techniques for drug therapy. Vitex negundo (V. negundo), a perennial herb belonging to the Varbanaceae family, is extensively used in conventional medication. To determine the existence of therapeutic components in leaf and callus extracts from wild V. negundo plants using gas chromatography-mass spectrometry (GC-MS). In this study, we conducted GC-MS on wild plant leaf extracts and correlated the presence of constituents with those in callus extracts. Various growth regulators such as 6-benzylaminopurine (BAP), 2,4-dichlorophenoxyacetic acid (2,4-D), α-naphthylacetic acid (NAA), and di-phenylurea (DPU) were added to plant leaves and in-vitro callus and grown on MS medium. The results clearly indicated that the addition of BAP (2.0 mg/L), 2,4-D (0.2 mg/mL), DPU (2.0 mg/L) and 2,4-D (0.2 mg/mL) in MS medium resulted in rapid callus development. The plant profile of Vitex extracts by GC-MS analysis showed that 24, 10, and 14 bioactive constituents were detected in the methanolic extract of leaf, green callus and the methanolic extract of white loose callus, respectively. Octadecadienoic acid, hexadecanoic acid and methyl ester were the major constituents in the leaf and callus methanolic extract. Octadecadienoic acid was the most common constituent in all samples. The maximum concentration of octadecadienoic acid in leaves, green callus and white loose callus was 21.93%, 47.79% and 40.38%, respectively. These findings demonstrate that the concentration of octadecadienoic acid doubles in-vitro compared to in-vivo. In addition to octadecadienoic acid; butyric acid, benzene, 1-methoxy-4-(1-propenyl), dospan, tridecanedialdehyde, methylcyclohexenylbutanol, chlorpyrifos, n-secondary terpene diester, anflunine and other important active compounds were also detected. All these components were only available in callus formed in-vitro. This study showed that the callus contained additional botanical characteristics compared with wild plants. Due to the presence of numerous bioactive compounds, the medical use of Vitex for various diseases has been accepted and the plant is considered an important source of therapeutics for research and development.

Montmorillonite K10-induced decomposition of methyl N-phenylcarbamate to phenylisocyanate and its prospect for recovering isocyanates from polyurethanes

The significant growth of the production and use of flexible polyurethane (PU) foam causes increased waste accumulation, thereby creating a demand for the recycling of PU. While upgrading PU materials to recycled polyols has been studied in detail, the recovery of diisocyanates is a longstanding challenge. Montmorillonite K10 (MK10) has been proposed as a catalyst to convert carbamates into isocyanates, but its prospects are unclear. Here, the MK10-catalyzed decomposition of methyl phenylcarbamate (MPC) into phenylisocyanate (PI) and the side product N,N’-diphenylurea (DPU) has been studied as a model reaction for the decomposition of PU foam and the potential recovery of PI. The effects of the amount of catalyst, the temperature, and the solvent were investigated by HPLC analyses. Kinetic analysis revealed that the uncatalyzed rate of the MPC decomposition is much lower than the catalyzed rate, indicating that the thermally driven decomposition is negligible. Our results, involving both experimental kinetic studies and models of the kinetics, show that, while MK10 effectively catalyzes the decomposition of MPC, it also causes the formation of aniline, which reacts with PI to form DPU. As a result, large amounts of MK10 favor DPU and prevent the selective formation of PI, and yields of PI >30 % were never observed. Likely, the OH groups of MK10 form covalent bonds with PI, causing a deficiency in the mole balance. Overall, MK10 is unsuited to provide high yields of isocyanates.

Electroanalysis of ethyl-centralite propellant stabiliser at magnetic nanoparticle modified glassy carbon and screen-printed electrodes with extension to forensic firearm residue analysis

Electroanalysis of organic residues of the propellant stabiliser ethyl-centralite (1,3 diethyl-1,3 diphenyl urea, EC) generated from the discharge of a weapon or improvised explosive devices is examined. Comparative effects of an electrode modifier, nanoparticles of magnetite (Fe3O4), on the sensor performance was of interest, with customised printed prototype development and analysis of organic firearm residue (OFAR) samples. Differential pulse voltammetry (DPV) calibration studies realised sensitivity of 6.37 × 10−2 μA∙μM−1 (over the concentration range 2.5–50 μM) at the magnetic nanoparticle modified electrode, representing a 1.65 fold signal increase relative to unmodified electrodes with limit of detection 4.39 µM. Inclusion of the OFAR co-existing diphenylamine (DPA) stabiliser realised signal discrimination and sensitivity of 7.49 × 10−2 and 5.49 × 10−2 μA∙μM −1 for DPA, and EC respectively, using DPV over the same range. The work culminated in the qualitative and quantitative analysis of propellant stabilisers in firearm residue acquired from a single base shotgun shell, with recovery from a target sample cloth, together with unburnt propellant, making promising first steps towards a customised screen-printed prototype for use by forensic professionals. Scanning electron microscopy/energy dispersive spectroscopy and atomic force microscopy were employed for particle confirmatory analysis.

Study on Synthesis and Performance of Methyl Diphenyl Urea Stabilizer

Diphenylamine (DPA), formyl chloride, and sodium hydride (NaH) as raw materials synthesize methyldiphenylurea stabilizer by alkylation reaction. The physical and chemical properties of methyldiphenylurea were characterized by nuclear magnetic resonance hydrogen spectrum (1HNMR), X-ray energy spectrum (EDS), Fourier transforms infrared spectroscopy (FT-IR) and differential thermal analysis (DTA). Thermal Decomposition Experiment of Nitrate Propellant Containing Stabilizer by Thermogravimetric Analysis (TGA), exploring the Effect of Different Stabilizers. The molecular surface electrostatic potential energy of methyl diphenyl urea, triphenylamine ( TPA ), dimethyl diphenyl urea (C2), and glycerol trinitrate were calculated by Materials Studio software. The interaction between the stabilizer and glycerol trinitrate molecule was studied. The results showed that the weight loss rate of methyl diphenyl urea was less than 0.1 % within 30 days, and the chemical stability was good. And its negative electrostatic potential energy is larger than that of C2 and TPA, its intermolecular binding ability with glycerol trinitrate is stronger, and its inhibition of nitrate decomposition stability is the best.

Visible-light induced degradation of diphenyl urea and polyethylene using polythiophene decorated CuFe2O4 nanohybrids

The present work reports facile synthesis of CuFe2O4 nanoparticles via co-precipitation method and formulation of its nanohybrids with polythiophene (PTh). The structural and morphological properties were investigated using fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscopy coupled with energy dispersive spectra (SEM-EDS) and UV–Vis spectroscopy. The band gap was found to decrease with increase in the loading of PTh and was found to be 2.52 eV for 1-PTh/CuFe2O4, 2.15 eV for 3-PTh/CuFe2O4 and 1.89 eV for 5-PTh/CuFe2O4. The nanohybrids were utilized as photocatalysts for visible light induced degradation of diphenyl urea. Diphenyl urea showed 65% degradation using 150 mg catalyst within 120 min. Polyethylene (PE) was also degraded using these nanohybrids under visible light as well as microwave irradiation to compare its catalytic efficiency under both conditions. Almost 50% of PE was degraded under microwave and 22% under visible light irradiation using 5-PTh/CuFe2O4. The degraded diphenyl urea fragments were analyzed using LCMS and a tentative mechanism of degradation was proposed.

Palladium-Catalyzed Carbonylation of Amines with Mo(CO)6 as the Carbonyl Source

Catalytic carbonylation of transition metals is widely used as an effective means to synthesize carbonyl-containing compounds. In this article, we introduce a method for the synthesis of N,N′-diphenyl urea and N-phenyl carbamate by transition-metal-catalyzed carbonylation. Here, we use Mo(CO)6 as a safe and stable carbonyl source to introduce the reaction to produce carbonylation products and achieve the selective formation of N,N′-diphenylurea and N-phenylcarbamate under mild conditions. Mechanistic investigations suggested that the reaction proceeded through sequential amine C–H bond activation, carbonyl insertion, nucleophilic attack, and oxidation of Pd(0) with Cu(OAc)2 to generate N-phenyl carbamate and N,N-diphenyl urea products. Moreover, the indenones obtained with Mo(CO)6 as a CO surrogate can be functionalized to form synthetic useful derivatives via an environmentally friendly way.

Synthesis, in silico and investigation of anti-breast cancer activity of new diphenyl urea derivatives: Experimental and computational study

Cancer is a complex disease that requires multidisciplinary treatment. One of the most common cancers is breast cancer, and these cancers are usually estrogen receptor-positive. Today, chemotherapy, as well as surgery, has an important place in the treatment of cancer. For this reason, serious research is carried out on the search for new chemotherapeutic drugs. Some of the drugs currently used in breast cancer are targeted at the estrogen receptor. As a result of the preliminary analyses carried out within our study's scope, five new diphenylurea derivative compounds that we predict will be targeted to the estrogen receptor were determined and synthesized. Chemical analyzes of the synthesized compounds were performed. In addition, in vitro analyzes were performed for their biological effects. In this context, it was determined that DPU2, one of the compounds applied to the estrogen receptor (+) breast cancer cell line, MCF-7, showed the cytotoxic effect. The IC50 value was determined, and it was determined that although it showed a cytotoxic effect on MCF-7 cells, it did not show severe cytotoxicity in healthy fibroblast cells. Then, LC3B, one of the autophagy indicators, and IL-1β, a proinflammatory cytokine, were examined immunohistochemically. Both LC3B and IL-1β expression were lower in the DPU2 applied group than in the control group. These findings supported that DPU2 has antitumor activity on MCF-7. In conclusion, in the light of in silico and in vitro analyses conducted within the scope of our study, it was determined that DPU2, one of the five phenyl urea derivative compounds I synthesized, has the potential to be a drug in the treatment of estrogen receptor (+) breast cancer. However, the study needs to be supported by in vivo and clinical studies.

Supramolecular Approach to Tuning the Photophysical Properties of Quadrupolar Squaraines.

In the present study, the influence of the hydrogen bonding for the one- and two-photon absorption of the prototypical squaraine dye is investigated with quantum chemistry tools. The central squaraine unit is bound by strong hydrogen bonds with 4-substituted N,N′-diphenylurea and, alternatively, N,N′-diphenylthiourea molecules, which affects to a high extend the properties of the squaraine electron accepting moiety, thus shifting its maximum absorption wavelength and enhancing the TPA cross section. The replacement of oxygen by sulfur atoms in the squaraine central ring, known to affect its photophysical behavior, is considered here as the way of modifying the strength and nature of the intermolecular contacts. Additionally, the influence of the oxygen-by-sulfur replacement is also considered in the N,N′-diphenylurea moiety, as the factor affecting the acidity of the N–H protons. The introduction of the sequence of the substituents of varying electron-donating or electron-withdrawing characters in the position 4 of N,N′-diphenyl(thio)urea subsystems allows to finely tune the hydrogen bonding with the central squaraine unit by further modification of the N–H bond characteristics. All of these structural modifications lead to the controlled adjustment of the electron density distribution, and thus, the properties affected such as transition moments and absorption intensity. Ab initio calculations provide strong support for this way of tailoring of one- or two-photon absorption due to the obtained strong hypsochromic shift of the maximum one-photon absorption wavelength observed particularly for thiosquaraine complexes and an increase in the TPA wavelength together with the increase in the TPA cross section. Moreover, the source of the strong modification of the thiosquaraine OPA in contrast to the pristine oxosquaraine upon N,N′-diphenyl(thio)urea substitution is determined. Furthermore, for the first time, the linear dependence of the non-additivity in the interaction energy on the Hammett substituent constant is reported. The stronger the electron-donating character of the substituent, the larger the three-body non-additive components and the larger their percentage to the total interaction energy.

6-Benzylamino purine outperforms Kinetin and Thidiazuron in ameliorating flower longevity in Calendula officinalis L. by orchestrating physiological and biochemical responses

Abstract In view of extending the relatively brief postharvest life of flowers by a range of technologies, the present study elucidates the implication of 6-benzylamino purine (BAP), kinetin (KN) and thidiazuron (TDZ) on postharvest performance and flower longevity of isolated flowers of Calendula officinalis. BAP and KN belong to adenine group cytokinins while as TDZ is a diphenyl urea compound having cytokinin like activity. The harvested flowers were supplemented with BAP, KN and TDZ at various concentrations viz., 25, 50, 75 and 100 µM at one day before anthesis (cup shaped) stage. The control was designated by a distinct set of flowers held in distilled water (DW). Our findings revealed substantial enhancement in flower longevity by application of various growth regulators as compared to the control. Vase solutions containing BAP and KN at 50 µM and TDZ at 75 µM (individually) were most effective in improving the longevity of cut Calendula flowers. Improvement in flower longevity was primarily associated with high membrane stability index (MSI), upregulated activities of various antioxidant enzymes viz., catalase (CAT), superoxide dismutase (SOD) and ascorbate peroxidase (APX), besides an attenuated lipoxygenase (LOX) activity in the petals. As compared to control, the treated flowers exhibited higher values of soluble proteins, total phenols and total sugars, besides lower α-amino acid content in the petal tissues. However, BAP outplayed TDZ and KN in improving the flower longevity of Calendula officinalis by maintaining higher physiological and biochemical stability in petals.

Mechanophore activation enhanced by hydrogen bonding of diarylurea motifs: An efficient supramolecular force‐transducing system

AbstractMacromolecules are efficient as mechanical transducers for mechanically induced chemical bond cleavage reactions. Although various classes of polymers have been studied as effective mechanical‐force transducers for mechanophores, alternatives to polymer chains, that is, small molecules, have rarely been studied. In this paper, the role of hydrogen bonding as small‐molecule mechanical‐force transducers for the activation of mechano‐responsive molecular units (mechanophores) in the bulk is investigated. The introduction of diarylurea linkage motifs, which are known as strong hydrogen bonding groups, enhances the mechanochemical activation of the fluorescent mechanophore tetraarylsuccinonitrile (TASN) as effectively as the attachment of a typical macromolecular transducer. Electron paramagnetic resonance measurements of mechanically activated TASN with diphenyl urea motifs demonstrate its higher carbon–carbon bond dissociation ratio compared to that of TASN without diphenyl urea motifs. This efficient supramolecular‐force‐transducing system represents a new concept in the field of mechanochemistry, namely, the enhancement of mechanochemical bond scission by simply changing the substituents of a mechanophore, even in small molecules.

Investigation of active sites using solid state 27Al and 31P MAS NMR in ceramic amorphous aluminophosphate materials prepared from different potassium salts of phosphate for the synthesis of diphenyl urea derivatives

Ceramic amorphous aluminophosphate (CAmAlP) catalysts were prepared by precipitation method using different phosphate salts of potassium such as KH2PO4, K4P2O7 and K2HPO4 as well as H3PO4. The prepared materials were characterized by PXRD, FT-IR, XPS, SEM, BET Surface area, NH3-TPD, 27Al NMR and 31P NMR analytical methods. The catalytic activity of the materials was checked in the synthesis of diphenyl urea (DPU) from aniline and diethyl carbonate, under refluxing conditions. Further, the general application of the catalysts was tested using various substituted anilines. The recyclability of the catalysts was also studied. Uncertainties in percentage yields were calculated to check the reproducible surface properties. The P-XRD, BET Surface area and NH3-TPD results indicated that the materials were amorphous with mesoporous texture, surface areas and acidities in the range 200–260 m2/g and 0.4–0.7 mmol/g respectively. 27Al NMR studies revealed that Al is present in three different coordination states such as tetrahedral, pentagonal and octahedral. The relative percentages of these Al sites depends on the type of the potassium precursor phosphate salt used. Both tetrahedral and pentagonal Al sites in conjunction with each other represented catalytically active sites. An increase in the pentagonal sites contributed to additional increments to the catalytic activity of CAmAlP. The catalyst prepared from KH2PO4 was found to be the best and demonstrated 96% DPU yield.

Foliar application of plant growth regulators modulates the productivity and chemical profile of damask rose (Rosa damascena Mill.) under mid hill conditions of the western Himalaya

Damask rose (Rosa damascena Mill.) is one of the most valuable aromatic crops used in the flavors, perfumery, cosmetics, and pharmacological industries. However, environmental conditions and plant nutrition plays a key role in the productivity of the crop. The study aimed to understand the effect of plant growth regulators on growth, yield, and quality profile of damask rose. Thus a field experiment was conducted at CSIR-Institute of Himalayan Bioresource Technology experimental farm, Palampur, India during 2018-19. The experiment consists of three growth regulators viz., methyl jasmonate (at 25, 50 and 75 μL L-1), diphenyl urea (at 10, 15 and 20 mg L-1), kinetin (at 25, 30 and 35 mg L-1), and control (deionized water) in randomized block design with three replications. Growth regulators significantly affected yield attributes, yield, and composition of essential oil. Number of flowers plant-1 (73.3) and fresh flower weight plant-1 (203.5 g) were significantly higher in diphenyl urea at 15 mg L-1 as compared with other treatments. Applications of diphenyl urea at 15 mg L-1, kinetin at 30 and 35 mg L-1 increased the fresh flower yield by 56.0, 41.6, and 35.8%, respectively, as compared with control. Essential oil content was significantly higher with methyl jasmonate at 50 μL L-1 and diphenyl urea at 15 mg L-1. Application of diphenyl urea at 15 mg L-1 and kinetin at 30 mg L-1 increased essential oil yield by 72.8 and 52.8%, respectively, as compared with control. A total of 26 essential oil compounds contributed to 79.6-83.8%. The biplots of principal component analysis also indicated the higher positive correlations among the major hydrocarbons and revealed that there is an inverse relationship between monoterpenes and hydrocarbon compounds. So, from the current study, we have concluded that as per the need for the aroma and perfumery industry, different plant growth regulators can be used to enhance fresh flower yield and quality of damask rose under the mid hill conditions of the western Himalaya.

Novel diphenyl urea derivative serves as an inhibitor on human lung cancer cell migration by disrupting EMT via Wnt/β-catenin and PI3K/Akt signaling

Targeted anti-tumor small molecules are considered to be promising candidates for cancer treatment. The novel diphenyl urea derivative (DUD) was synthesized by the molecular docking based on the structure optimization of Taspine (a natural product). In this study, we explored the anti-metastatic potential of DUD for NSCLC in vitro. DUD significantly suppressed A549 cell migration by reversing EMT. The inhibition was reflected on upregulation of E-cadherin and downregulation of N-cadherin, vimentin, Snail and HIF-1α. Meanwhile, DUD inhibited the β-catenin nuclear translocation by upregulating Axin and downregulating the expression of APC, CK1 and phosphorylation of GSK3β, and simultaneously decreasing MMP9 and MMP13 expression. Moreover, it was associated with the downregulation of the PI3K/Akt/mTOR signaling. Furthermore, we used XAV939, an β-catenin inhibitor, to verify the mechanism of DUD. These results suggested that DUD inhibited A549 cells migration by reversing EMT via Wnt/β-catenin and PI3K/Akt signaling. DUD might be a potential therapeutic drug candidate for NSCLC treatment.

Research Progress of Diphenyl Urea Derivatives as Anticancer Agents and Synthetic Methodologies

The malignant neoplasm, which is recognized as cancer, is a serious threat to human health and frequently-occurring disease. Diphenylurea, an important link structure in the design of active substance for treating cancer due to its near-perfect binding with certain acceptors, has demonstrated many activities against several human cancer cell lines. Various novel compounds with diphenyl urea as anticancer agents were constructed with the successful development of sorafenib. Diphenylurea is utilized to treat cancer by inhibiting cell signaling transduction, such as RAS-RAFMEK- ERK signaling pathway and PI3K-Akt-mTOR pathway. In addition, this structure inhibits tumor cell growth by inhibiting receptor tyrosine kinases multiply, such as Vascular Endothelial Growth Factor Receptors (VEGFRs), Platelet-Derived Growth Factor Receptors (PDGFRs), Epidermal Growth Factor Receptors (EGFRs). It regulates the pH value in cells by inhibiting CAIX/XII and to achieve cancer therapeutic effect. Besides, the diphenyl urea structure is applied to the synthesis of reagents like Aurora kinases inhibitors and HDAC inhibitors that affect cell division and differentiation to treat cancer. To reach the goal of treating tumor, this structure is also used as a DNA-directed alkylating agent by affecting the expression of genes. An application of the most representative diphenyl urea derivatives as antitumor agents is summarized in this review, focusing on their mechanisms bound to the targets. Meanwhile, the progress of researches on methods of synthesizing diphenyl urea derivatives is provided.

Investigation on the nature of catalytically active sites in non-crystalline aluminophosphates from 27Al and 31P MAS-NMR studies

Amorphous aluminophosphate (AmAlPO4) materials were synthesized by conventional precipitation technique from different phosphate precursors (Na4P2O7, NaH2PO4, Na2HPO4, (NH4)H2PO4, (NH4)2HPO4 and H3PO4) without using any structure directing agents. All the prepared materials were analyzed by 27Al and 31P MAS-NMR, PXRD, FT-IR, XPS, BET, NH3- TPD and SEM-EDS. The catalytic activity of the materials was checked for synthesis of diphenyl urea (DPU). Phosphoric acid (H3PO4) as a precursor was found to be more active catalyst (which yielded 90% of DPU) than the salt forms. 27Al and 31P MAS-NMR studies showed the presence of variable percentages of tetra and penta coordinated Al species, which are attributed to the catalytic activity of AlPO4. AmAlPO4 materials prepared were amorphous having intrinsic mesoporosity, moderate surface area and moderately strong acidic sites. A synergetic combination of all these surface properties play a subtle role in determining the activity of the differently coordinated Al species in the catalysts.

L-Proline Catalyzed Synthesis of Various N-substituted Urea and Unsymmetrical N,N’-disubstituted Urea

Here, we report a simple and efficient method for the synthesis of different unsymmetrical N,N’-disubstituted urea and N-substituted urea derivatives using L-Proline as a green catalyst. The methodology is applicable for synthesizing various derivatives of phenylurea, diphenyl urea with excellent yield at mild condition.