N-methyl Urea Research Articles

In-vivo anticancer activity of biosynthetic silver nanoparticles of Cassia marginata Roxb against NMU-Induced mammary carcinoma

The use of silver nanoparticles in the diagnosis and treatment of cancer is on the rise, and they are becoming more commonly recognized as effective therapeutic agents. Silver nanoparticles of Cassia marginata Roxb were prepared to investigate its anticancer potential in female Sprague-Dawley rats against N-nitroso N-methyl urea-induced mammary carcinoma. In this study, thirty animals were divided into five groups of six each: normal, disease control, Cassia marginata silver nanoparticles at 200 mg/kg, 400 mg/kg, and tamoxifen 10 mg/kg. N-nitroso N-methyl urea (50 mg/kg, i.p) was given twice at 52 days of age and four weeks after the prior treatment in 0.9 % NaCl. A total of two oral doses of Cassia marginata silver nanoparticles were administered, and the results were compared to the results of a single dose of tamoxifen (10 mg/kg, p.o). The tumor incidence rate, average tumor burden, and the total number of tumors were reduced in the treatment groups when compared with the disease control and the silver nanoparticles of Cassia marginata may prevent mammary carcinoma in Sprague-Dawley rats when exposed to N-nitroso N-methyl urea.

The anti-cancer potential of 2,4,6 tris-methyphenylamino1,3,5-triazine compound against mammary glands cancer: Via down-regulating the hormonal, inflammatory mediators, and oxidative stress

Aim of the studyBreast cancer is caused by abnormal growth of the cells and progressed due to the over-expression of estrogen (ER) and progesterone (PR). The current study was designed to evaluate the anti-tumor activity of 2,4,6 tris-methyphenylamino1,3,5-triazine compound (MPAT) in N-nitroso, N-methyl urea (NMU)-induced mammary gland cancer. MethodsMolecular docking and in-vitro studies were conducted before the in-vivo analysis. Female Albino rats were divided into 5 groups (n = 6). Group I received Carboxymethylcellulose (CMC) (1 mL/100 g). Group II (diseased group) received NMU 50 mg/kg. Group III (standard group) received tamoxifen (5 mg/kg). Group IV–V received MPAT at doses of 30 and 60 mg/kg respectively. All groups received NMU intraperitoneally except the control group at 3 weeks intervals for 12 weeks. After 12 weeks of NMU dosing, MPAT was given for 15 consecutive days. Biochemical, oxidative stress markers, hormonal profile, and inflammatory mediators were analyzed. Key findingsMPAT showed significant interaction with the selected targets in docking studies. An over-expression of ER and PR was observed in NMU-treated rats which were restored significantly after MPAT administration. Nitrite and MDA levels were high in the diseased group and MPAT treatment attenuated the oxidative damage after treatment. Antioxidants such as superoxide dismutase (SOD), Catalase (CAT), total sulfhydryl (TSH), glutathione (GSH), and Lactate dehydrogenase (LDH) values were low in NMU-treated rats. SignificanceThis study concluded that MPAT can be used as an anticancer agent due to its significant effects on down-regulating the hormonal profile and oxidative stress markers.

Ionic Liquid Analogs of AlCl3 with Urea Derivatives as Electrolytes for Aluminum Batteries

AbstractThe ionic liquid analog, formed through the mixture of urea and AlCl3, has previously shown to serve as a low‐cost electrolyte for an aluminum‐graphite battery, while maintaining good performance and achieving high Coulombic efficiency. Undesirable are the relatively high viscosity and low conductivity of this electrolyte, when compared to chloroaluminate ionic liquids with organic cations. In this work, the fundamental changes to the electrolyte resulting from using derivatives of urea (N‐methyl urea and N‐ethyl urea), again mixed with AlCl3, are examined. These electrolytes are shown to have significantly lower viscosities (η = 45, 67, and 133 cP when using N‐ethyl urea, N‐methyl urea, and urea, respectively, at 25 °C). The associated batteries exhibit higher intrinsic discharge voltages (2.04 and 2.08 V for N‐methyl urea and N‐ethyl urea electrolytes, respectively, vs 1.95 V for urea system@100 mA g−1 specific current for ≈5 mg cm−2 loading), due to changes in concentrations of ionic species. Aluminum deposition is directly observed to primarily occur through reduction of Al2Cl7− when AlCl3 is present in excess, in contrast to previously suggested cationic Al‐containing species, via operando Raman spectroscopy performed during cyclic voltammetry.

Polarity-dependent extraction of flavonoids from citrus peel waste using a tailor-made deep eutectic solvent

Choline chloride-based deep eutectic solvents (DESs) were used as green alternatives to conventional organic solvents for extracting valuable flavonoids from citrus peel waste. The effects of viscosity, pH, and polarity of DESs on the extraction efficiency were investigated. Results revealed linear dependence of extraction yield of citrus flavonoids on the polarity of the hydrogen bond donor (HBD). To simultaneously and effectively extract polymethoxylated flavonoids (PMFs) and glycosides of flavonoids (GoFs) with different polarities, five ternary DESs were designed and prepared by combining the effective HBD components. Among the tailor-made DESs studied, choline chloride–levulinic acid–N-methyl urea showed the highest extraction yield of total flavonoids. Under optimized extraction conditions, 18.75 mg/g PMFs and 47.07 mg/g GoFs were extracted from citrus peel with recoveries of 95.87% and 86.32%, respectively. This study presents a useful strategy based on tailor-made DESs to selectively extracted value-added flavonoids from waste peels in the citrus-processing industry.

Palliative Role of Aqueous Ginger Extract on N-Nitroso-N-Methylurea-Induced Gastric Cancer

Ginger (Zingiber officinale) is a spice and also an herbal medicine used worldwide for managing GI tract disturbances. However, its role in gastric cancer is sparingly known. This study ensures the standardization of gastric cancer by the induction of N-nitroso N-methyl Urea (MNU) and to determine the role of the aqueous extract of ginger (AGE) in MNU-induced gastric cancer in albino Wistar rats. Accordingly, the anticancer potential of AGE and its possible mode of action were assessed on rats exposed to MNU, by various biochemical and molecular assays. As evidenced by the extent of lipid peroxidation, gastrin levels and histopathological sections in MNU-induced cancerous lesions at 8 wk which was stabilized at 16 wk confirming the induction of gastric carcinoma by the chemical carcinogen. Further, results revealed that AGE alleviated the oxidative stress as evidenced by the stomach antioxidant enzymes (SOD, catalase, GPx, and GR), markers of oxidative stress (TRx, GRx) and Gastrin, a specific marker for gastric cancer and a decreased level of pro-inflammatory markers (NF-kB, TNF-α, IL-6, PGE2) which was further confirmed by histopathological analysis. AGE is responsible to mitigate oxidative stress and inflammation related to gastric cancer and could be used as a potential dietary intervention in gastric cancer therapy.

Rearranged Terpenoids from the Marine Sponge Darwinella cf. oxeata and Its Predator, the Nudibranch Felimida grahami.

Marine sponges are a rich source of terpenoids with rearranged spongian carbon skeletons. Investigation of extracts from the sponge Darwinella cf. oxeata yielded four new rearranged diterpenoids, oxeatine (2) and oxeatamides H-J (3-5), as well as the known metabolites oxeatamide A (6), oxeatamide A methyl ester (7), and membranolide (1). Oxeatine (2) has a new heterocyclic skeleton, while oxeatamide J (5) has an N-methyl urea group included in a γ-lactam moiety. UPLC-QTOF analysis of the extract obtained from the mantle of the nudibranch Felimida grahami indicated the presence of 1 and 4.

Trimorphism of N-methylurea: crystal structures, phase transitions and thermodynamic stabilities

Melt crystallization of N-methylurea (NMU) was investigated by X-ray and differential scanning calorimetry (DSC) techniques. In addition to the known orthorhombic stable Form I, two new polymorphic forms (II and III) crystallizing in the centrosymmetric space group P21/c were obtained at different quenching temperatures. The crystal structures of Forms II and III were determined from X-ray powder diffraction data. The crystallographic results for the monoclinic forms are presented in this study, as well as a detailed comparison of crystal structures of the three polymorphs. The nature of hydrogen bonds in Form II and Form III were found to be similar; hence, a first order mechanism governed by means of shear movements is suggested where a transition via nucleation and growth could occur at low temperatures. The relative thermodynamic stabilities of the three forms of NMU were investigated by DSC analyses. Form II and Form III exhibited a reversible solid–solid phase transition at circa −118 °C. Both forms were found to be monotropically related to the stable Form I.

Anticancer Activity of Ethyl Acetate Root Extract of Xanthium strumarium Linn. in N-Nitroso N-Methyl Urea Induced Mammary Carcinoma in Female Sprague-Dawley Rats

The objective of the study was to evaluate the anticancer activity of ethyl acetate root extract of Xanthium strumarium Linn. (EAREXS) in N-Nitroso N-methyl urea (NMU) induced mammary carcinoma in female Sprague-Dawley rats. Thirty virgin female Sprague-Dawley rats of 55 day old were divided into five groups (normal control, disease control, EAREXS 200 mg/kg, EAREXS 400 mg/kg, tamoxifen10 mg/kg) of six animals each. The mammary carcinoma was induced by two intraperitoneal doses of N-Nitroso N-methyl urea (NMU) (50mg/kg/body weight each) in 0.9% NaCl (maintained at 4°C) at 55 day of age and 4 week after the prior administration. The drug EAREXS was administered in two doses, 200 mg/kg, and 400 mg/kg orally and compared with the oral dose of tamoxifen (10 mg/kg). EAREXS 200 mg/kg, 400 mg/kg, and tamoxifen10 mg/kg decreased the tumor incidences by 50%, 66.67%, and 83.33% and the total number of tumors in group by 46.15%, 69.23% and 92.30% respectively, when compared to the disease control. EAREXS 200 mg/kg, 400 mg/kg, and tamoxifen10 mg/kg decreased the average tumor burden by 68.61%, 86.65% and 94.91% and average tumor volume by 66.45%, 82.01%, and 92.98% respectively, when compared to disease control group. The results concluded that EAREXS prevent the mammary carcinogenesis induced by N-Nitroso N-methyl urea in female Sprague-Dawley rats.

Hydrothermal synthesis of hollow Ca2Ge7O16microspheres as high-capacity anodes for Li-ion batteries with long cycling life

Urchin-like Ca2Ge7O16 hollow spheres have been successfully synthesised by hydrothermal methods assisted with urea or N-methyl urea. When tested as anode materials, the as-obtained urchin-like hollow spheres consisting of nanorods with diameters of about 20 nm could deliver a capacity of 603 mA h g−1 after 200 cycles at a current density of 1000 mA g−1.

β‐cyclodextrin‐capped palladium nanoparticle‐catalyzed ligand‐free Suzuki and Heck couplings in low‐melting β‐cyclodextrin/NMU mixtures

Low‐melting β‐cyclodextrin/N‐methylurea (NMU) mixture, an efficient catalytic system for ligand‐free Suzuki and Heck couplings in the presence of fresh native β‐CD‐capped Pd0 nanoparticles, has been successfully reported. This natural and convenient system can be performed in air and could afford the corresponding cross‐coupled products in good to excellent isolated yields after a simple workup under every low Pd loading (0.05 mol%). Remarkably, the catalytic system can be recycled and reused without loss of catalytic activity. Copyright © 2014 John Wiley & Sons, Ltd.

Molecular and Supramolecular Origins of Optical Nonlinearity in N-Methylurea

The delicate balance between solid-state intermolecular interactions and electron-donating methyl-group influences in N-methylurea (NMU) is shown to distinguish its nonlinear optical properties, relative to those of urea, a standard reference material for second harmonic generation (SHG). The solid-state intermolecular interactions in NMU are identified using neutron diffraction data, showing that hydrogen bonding generates an extensive 3D supramolecular network of NMU molecules with secondary and tertiary nonbonded contacts helping to hold this network in a closely packed form. The undulating “urea tape” motif within this network renders an overall packing arrangement that is less SHG-favorable than that of urea, which exhibits a more head-to-tail molecular alignment. The primary, secondary, and tertiary nonbonded contacts are classified using graph-sets, Hirshfeld surfaces, and fingerprint plots. H···H contacts in NMU contribute to the overall Hirshfeld surface area much more than in urea, forming at th...

Curcumin Regulates Colon Cancer by Inhibiting P-Glycoprotein in In-situ Cancerous Colon Perfusion Rat Model

Studies on p-glycoprotein was carried out world vide with cell lines like Caco2, MDR1-LLC-PK1 and MDR1-MDCK in-vitro, but most of the results were failed to produce similar results in-vivo. In the present study curcumin inhibitory action on p-glycoprotein increased permeability of irinotecan, so in the colon cancer it would be beneficial if curcumin used as add on therapy. Intra-rectal administered of N-Nitroso N-methyl urea (2 mg/Kg) induced colon cancer. Single pass whole length of colon in-situ perfusion was carried out in rats with irinotecan to study the influence of p-glycoprotein modulators like verapamil and curcumin. The rats were divided in to 5 groups (n=6), Group I served as control perfused with 30 μg/ml of irinotecan, propronolol and phenol red. Group II was cancerous group, induced by N-methyl N-nitroso urea. Group III was perfused with irinotican in cancerous rats. Group IV, perfused with irinotican in presence of verapamil and group V was pre-treated with curcumin and then perfused with irinotican and was estimated by HPLC-UV to effective permeability coefficient. Our qRT-PCR and Western blot results confirmed that about 15-fold decreases in the expression of p-glycoprotein (P-gp) in curcumin treated colon cancer cells. Irinotecan was increased to 0.00066 cm/s and about 11-fold increase in verapamil-coperfused group, where curcumin pre-treated group irinotecan was increases 0.00006 cm/s to 0.00042 cm/s that is about 7-fold increase p-glycoprotein inhibitory activity by verapamil and curcumin found to be significantly enhanced the cancerous colon permeability of irinotecan. Any safe suitable p-glycoprotein inhibitors along with irinotecan will enhance the therapeutic benefit in the treatment of the colon cancer.

Chemopreventive effect of montelukast in n-nitroso n-methyl urea induced mammary carcinogenesis in female Sprague-Dawley rats

Objective:The objective of the study was to evaluate the chemopreventive effect of montelukast sodium; selective reversible cysteinyl leukotriene D4-receptor antagonist in N-nitroso N-methyl urea (NMU) induced mammary carcinogenesis in virgin female Sprague-Dawley rats.Materials and Methods:Thirty rats were divided into five groups (normal control, disease control, montelukast1 mg/kg, montelukast10 mg/kg, tamoxifen10 mg/kg) of six animals each. The drug was administered in two doses,1 mg/kg,and 10 mg/kg orally and compared with the standard drug tamoxifen (10 mg/kg)p.o.Results:Montelukast sodium 1 mg/kg,10 mg/kg, and tamoxifen10 mg/kg decreased the tumor incidences by 50%,66.67%, and 83.33% and the total number of tumors in group by 41.67%, 58.33% and 91.67% respectively, when compared to the disease control. Montelukast sodium 1 mg/kg,10 mg/kg,and tamoxifen10 mg/kg decreased the average tumor burden by 86.41%,94.8% and 95.97%and average tumor volume by 89.52%, 95.84%, and 95.4%respectively, when compared to disease control group.Conclusion:The results revealed that montelukast sodium prevent the mammary carcinogenesis and confirms the role of cysteinyl leukotriene D4-receptor in mammary gland neoplasia.

A Somaclonal Variant of Rose-Scented Geranium (Pelargonium spp.) with Moderately High Content of Isomenthone in its Essential Oil

Rose-scented geranium (Pelargonium spp.), which is highly valued for its essential oil, is exclusively propagated vegetatively. Hence no genetic improvement work is possible through conventional breeding. Somaclonal variation was generated with and without in vitro mutagenesis using N-nitroso-N-methyl urea (NMU) in an Indian cultivar 'Bourbon', and a clone 'Narmada'. A somaclonal variant (N75) with a moderately high content of isomenthone in its essential oil was isolated from somaclones generated after treatment of internodal explants of clone, 'Narmada' with 0.25 mM NMU for 1 h. The contents of isomenthone in its essential oil were 26% and 35%, respectively, in SC2/VM2 and SC3/VM3 generations (second and third vegetative generations, respectively, after in vitro mutagen treatment) as compared with 0.7% and 0.3%, respectively, in the parental clone, 'Narmada'. The contents of alcohols and their esters (linalool, citronellol, geraniol, citronellyl formate and geranyl formate) in the essential oil of N75 in SC2/VM2 and SC3/VM3 generations were 49% and 35%, respectively, as compared with 69% and 63%, respectively, in the parental clone, 'Narmada'. This is the first report on a chemovariant of rose-scented geranium with a moderately high content of isomenthone. All earlier reported isomenthone-rich variants of rose-scented geranium had quite high contents of isomenthone (64-71%) in their essential oils. The probable modes of origin of this somaclonal variant, its parental clone 'Narmada' (with very low content of isomenthone) and four earlier reported isomenthone-rich variants of Indian cultivars of geranium are discussed.

A Novel Biginelli-Like Reaction: An Efficient One-pot Synthesis of Spiro[oxindole-quinazoline/pyrimidine]ones

Some new spiro[oxindole-quinazoline/pyrimidine]ones were synthesized via a novel three-component Biginelli-like reaction between isatin, cyclic or acyclic 1,3-dicarbonyl compounds, and urea, N-methyl urea or thiourea in one pot and good yields.

A stochastic model for the critical length of a spiral edge

We adopt a stochastic viewpoint for the critical length l c of an edge on the side of a spiral of a crystal growing from solution at low supersaturations. It is argued that the nature of the critical length arises from a transition caused by a dynamical exchange as molecules at the edge go from a “fluid-like” coordination to a crystalline coordination. The expression for the critical length derived from such a mechanism exhibits a dependence on the energy or work required to remove a molecule from a kink site to the crystal terrace and on the supersaturation. Predictions of l c by our model compare well to stochastic simulations of spirals of a Kossel crystal, and provide reasonable order-of-magnitude estimates of spiral behavior of n-methyl urea growing from methanol.

A New Record for Negative Solvatochromism

The authors report the synthesis and properties of a pyridinium-barbiturate-betaine dye (3). After reacting diethylphenyl malonate and N-methyl urea they perform a nitration leading to 2. The following reaction with potassium formate followed by 2,4,6-triphenylpyrilium tetrafluoroborate yields the desired dye 3.

Dielectrophoretic field-flow fractionation system for detection of aquatic toxicants.

Dielectrophoretic field-flow fractionation (dFFF) was applied as a contact-free way to sense changes in the plasma membrane capacitances and conductivities of cultured human HL-60 cells in response to toxicant exposure. A micropatterned electrode imposed electric forces on cells in suspension in a parabolic flow profile as they moved through a thin chamber. Relative changes in the dFFF peak elution time, reflecting changes in cell membrane area and ion permeability, were measured as indices of response during the first 150 min of exposure to eight toxicants having different single or mixed modes of action (acrylonitrile, actinomycin D, carbon tetrachloride, endosulfan, N-nitroso- N-methylurea (NMU), paraquat dichloride, puromycin, and styrene oxide). The dFFF method was compared with the cell viability assay for all toxicants and with the mitochondrial potentiometric dye assay or DNA alkaline comet assay according to the mode of action of the specific agents. Except for low doses of nucleic acid-targeting agents (actinomycin D and NMU), the dFFF method detected all toxicants more sensitively than other assays, in some cases up to 10 (5) times more sensitively than the viability approach. The results suggest the dFFF method merits additional study for possible applicability in toxicology.

Ionic liquid phase organic synthesis (IoLiPOS) methodology applied to the preparation of new 3,4-dihydropyrimidine-2(1H)-ones bearing bioisostere group in N-3 position

Abstract The ionic liquid phase organic synthesis (IoLiPOS) methodology has been used for the preparation of new 3,4-dihydropyrimidine-2(1H)-ones (DHPMs) bearing bioisostere group in N-3 position. For the 3,4-DHPMs substituted with various thiazole rings, the strategy involved a three-component Biginelli condensation in the second step with good yields (93–96%) from ILP bound acetoacetate, aromatic aldehyde (93–97% yield), and N-methyl urea followed by N-3 alkylation with chloroacetonitrile on the ILP bound 3,4-DHPM. Quantitative thionation of the nitrile group grafted on the ILP bound 3,4-DHPM was realized in MeOH with a 40–48% solution of ammonium sulfide and subsequent addition of α-bromoketone produced the thiazole ring appended on the 3,4-DHPM core. After cleavage by transesterification, the target compounds were obtained in good overall yields (47–50%). The efficiency of the IoLiPOS methodology was also demonstrated by the preparation of new 3,4-DHPMs with a tetrazole ring in N-3 position in 5 steps (53–61% overall yield) via the ILP bound 3-cyanomethyl 3,4-DHPM as key intermediate.

Dietary soy protein inhibits DNA damage and cell survival of colon epithelial cells through attenuated expression of fatty acid synthase

Dietary intake of soy protein decreases tumor incidence in rat models of chemically induced colon cancer. We hypothesized that decreased expression of fatty acid synthase (FASN) underlies, in part, the tumor-preventive effects of soy protein, since FASN overexpression characterizes early tumorigenesis. Here, we show that colonic FASN levels are reduced with dietary intake of soy protein isolate (SPI), compared with a control casein diet, in male Sprague-Dawley rats administered the colon carcinogen azoxymethane. SPI consumption resulted in decreased serum insulin levels and decreased azoxymethane-induced tumor suppressor p53 phosphorylation in colon crypt epithelium. To evaluate potential links between insulin and FASN leading to DNA damage, C2(BBe)1 colon epithelial cells, treated with insulin and/or the carcinogen N-nitroso-N-methylurea (NMU), were evaluated for DNA damage and apoptosis after transfection with control or FASN small interfering RNAs (siRNAs). While the numbers of DNA apurinic/apyrimidinic sites (biomarker of DNA damage) induced by NMU were unaffected by transfection of FASN siRNA, insulin induction of these sites was decreased with FASN knockdown. By contrast, NMU-induced apoptosis of C2(BBe)1, as well as intestinal epithelial cell (IEC)-6, was enhanced by transfected FASN siRNA. Increased FASN expression in IEC-6 cells by addition of liver X receptor agonist T0901317 did not affect apurinic/apyrimidinic site number, but enhanced cell killing by cerulenin, a FASN inhibitor. Moreover, insulin rescued NMU-treated cells from apoptosis in an FASN-dependent manner. Results suggest that dietary SPI, by decreasing circulating insulin levels and colon FASN expression, attenuates insulin-induced DNA damage and FASN-mediated anti-apoptosis during carcinogenesis, resulting in an overall reduced tumorigenic state.