Simulation of the oxidative metabolization pattern of netupitant,an NK1 receptor antagonist,by electrochemistry coupled to mass spectrometry

Considering the frequent use of netupitant in polytherapy,the elucidation of its oxidative metabolization pattern is of major importance.However,there is a lack of published research on the redox behavior of this novel neurokinin-1 receptor antagonist.Therefore,this study was performed to simulate the intensive hepatic biotransformation of netupitant using an electrochemically driven method.Most of the known enzyme-mediated reactions occurring in the liver(i.e.,N-dealkylation,hydroxylation,and Noxidation)were successfully mimicked by the electrolytic cell using a boron-doped diamond working electrode.The products were separated by reversed-phase high-performance liquid chromatography and identified by high-resolution mass spectrometry.Aside from its ability to pinpoint formerly unknown metabolites that could be responsible for the known side effects of netupitant or connected with any new perspective concerning future therapeutic indications,this electrochemical process also represents a facile alternative for the synthesis of oxidation products for further in vitro and in vivo studies.

Correction:Making the Complicated Simple:A Minimizing Carrier Strategy on Innovative Nanopesticides

The Nano-Micro Letters(2024)16:193,article by Shangguan et al.,entitled“Making the Complicated Simple:A Minimizing Carrier Strategy on Innovative Nanopesticides”(Nano-Micro Lett.https://doi.org/10.1007/s40820-024-01413-5),was published online on 14 May,2024,with errors.The structural formulas and captions of the three acyl chlorides in Fig.3A were wrong.They should be as shown below.

Triterpenoid of avocado (Persea americana) seed and its cytotoxic activity toward breast MCF-7 and liver HepG2 cancer cells

Objective:To determine the structure of triterpenoid isolated from avocado seeds and the cytotoxic effect on MCF-7 and Hep G2 cells.Methods:The powder sample was macerated with ethanol,followed with separation of the extract by column chromatography.The target compound was monitored on thin layer chromatography plate and reagent Lieberman–Buchard.The isolated compound was characterized by spectral analysis,mainly ultraviolet,infrared,and liquid chromatographymass spectroscopy and their spectroscopic data with those reported in literature were compared.In vitro cytotoxic activity was investigated against Vero,MCF-7,and Hep G2 cell lines using MTT assay.Results:A triterpenoid compound was isolated from ethanol extract.The extracts,fraction(F3),and the isolated compound showed a significant cytotoxic activity against all investigated cell lines.MTT assay showed that the triterpenoid isolate inhibited cell proliferation of MCF-7 and Hep G2 cell line with the IC50 values of 62 mg/m L and 12 mg/m L,respectively,and was safe to normal cells.Conclusions:The results of the present study reveal that triterpenoid from avocado seeds have the potential for further development as anticancer agents.

Study on the Structure of Supramolecular Inclusion Complex of β-Cyclodextrin with Retinoic Acid

Inclusion compound of retinoic acid with (-cyclodextrin was prepared by coprecipitating method, the structure of resulting product was studied by elemental analysis, differential scanning caloriemetry(DSC) analysis, FT-IR spectroscopy and X-ray diffractometry, and the formed supramolecule self-assembles in aqueous solution according to molar ratio 2:1 of host-guest.

Toxicological studies for some agricultural waste extracts on mosquito larvae and experimental animals

Objective:To evaluate some agricultural waste extracts as insecticide and their effects on enzyme activities in liver and kidney of male mice.Methods:The insecticidal activity of five tested compounds(one crude extract and 4 waste compounds) was bioassay against the 3rd instars of the Culex pipiens(Cx.pipiens) larvae in the laboratory.The LC_(50) values of eucalyptol,apricot kernel.Rice bran,corn,black liquor and white liquor are 91.45.1166.1,1203.3.21449.65.4025.78 and 6343.18 ppm,respectively.Selection of the compounds for the subsequent studies was not only dependent on LC_(50) values but also on the persistence of these wastes products on large scale.Results:White and black liquor did not produce any gross effect at 200 mg/Kg body weight.No apparent toxic symptoms were observed in tested animals during the whole period of the experimenl which run out for 14 days.No statistically significance was observed in the enzyme choliuesterase activity,the activities of liver enzymes and kidney function in treated mice with black and while liquors.While,no and slighl inhibition was observed after the 2weeks ol treatment period with deltamethrin and lenilrothion reached to about 24%in plasma cholinesterase enzyme activity.Significantly increase in the activities ol liver enzymes and kidney function in treated mice with deltamethrin and fenitrothion.Conclusions:Black liquor can be used efficiently In control Cx.pipiens larvae under laboratory condition.Environmental problem caused by rice straw can be solved by converting the waste material to beneficial natural selective insecticide.

Polydentate cyclotriphosphazene ligands:Design,synthesis and bioactivity

Five multinuclear cyclotriphosphazene ligands were synthesized and tested for their cleavage activities to plasmid DNA. All of these new compounds were confirmed by MS, ^1H NMR, ^31P NMR, ^13C NMR and IR. Preliminary studies on the cleavage of pUC19 DNA in the presence of metal complexes were performed. The results revealed that these complexes could act as powerful catalysts under physiological conditions. The complexes 3b ＋ Cu can effectively cleave DNA to nicked form, giving hydrolysis rate constant of 0.08/h under physiological conditions. An acid-base catalyzed DNA phosphate-diester hydrolysis mechanism was also orooosed.

Potent Anticonvulsant 1H-Imidazol-5(4H)-One Derivatives with Low Neurotoxicity

We report here the synthesis and in vivo anticonvulsant/neurotoxicity activities of a series of compounds belonging to 2-aryl-4-arylidene-1-phenyl-1H-imidazol-5(4H)-one. The scaffold is based on the commonality of 5-membered lactam ring structures as successful anticonvulsant agents. The present compounds exhibited a range of anticonvulsant activity in pentylenetetrazole (PTZ)-induced seizure test. In particular, the protection was excellent by compounds bearing furylmethylidene on C4, possibly due to good pharmacokinetic properties. It was found that high lipophilicity and/or electron deficient aryl ring substitution at C4 compromised the anticonvulsant activities. For example, chloro analogues were found much less active than unsubstituted phenyl or furyl derivatives. Regarding side effects, active compounds exerted no observable neurotoxic effect at their therapeutic doses in Chimney test.

An altemative synthetic approach towards erythrinan and homoerythrinan alkaloids by tandem semipinacol/intramolecular Schmidt reaction

An alternative construction of A-B-D ring-system of erythrinan and homoerythrinan alkaloids by TiCl4-mediated tandem semipinacol/intramolecular Schmidt reaction of α-siloxyepoxyazide was addressed and the unusual epoxidation stereoselectivity was observed in preparation of the substrate once again.

Insight of ZnS nanoparticles contribution in different biological uses

Objective:To evaluate the contributions of the some quantum dots in different biological uses in order to valorizes such nanomaterials for further applications.Methods:Zinc sulfide ZnS nanoparticles were synthesized in aqueous medium at pH constant,the obtained nanoparticles has been characterized by X-ray diffraction(XRD),transmission electron microscopy(TEM)and Fourier Transform Infra-red(FTIR) spectroscopies.Zinc sulfide nanoparticles were screened for their antibacterial and antifungal profiling and tested for antioxidant activity using l,l-diphenyl-2-picrylhydrazyl(DPPH),hydroxyl radical(OH·) and hydrogen peroxide(H_2O_2) scavenging activity,ferric reducing power(FRP) assay and ferrous ion chelating(FIC)methods.Results:The sizes of the crystallites were estimated to 3 nm using the DebyeScherrer formula based on the XRD data.The shape was identified to be quasi-spherical whith agglomerated particles.The obtained ZnS quantum dots present an antioxidant activity especially in oxido-reduction power,and can be used for species profiling either for bacteria and fungus.Conclusion:It was found that ZnS nanoparticles showed relatively higher antioxidant activities and antibacterial with an antifungal behavior which proves that this nanomaterials can react at the interface with the life entities.

Removal of Cu(II),Pb(II),Mg(II),and Fe(II) by Adsorption onto Alginate/Nanocellulose Beads as Bio-Sorbent

Alginate blended with cellulose nanocrystals(CNC),cellulose nanofibers(CNF),and tri-carboxylate cellulose nanofibers(TPC-CNF)prepared and encapsulated in the form of microcapsules(bio-polymeric beads).The cellulosic nanomaterials that used in this study were investigated as nanomaterials for wastewater treatment applications.Batch experiments were performed to study the removal of copper,lead,magnesium,and iron from aqueous solutions by the prepared beads.The effects of the sorbent dosage and the modified polymers on the removing efficiency of the metal cations were examined.Atomic absorption was used to measure the metal ions concentrations.The modified bio-polymeric beads(Alg-CNF,Alg-CNC,and Alg-TPC-CNF)exhibited high-efficiency towards removing of the metal cations;Cu^(2+),Pb^(2+),Mg^(2+),and Fe^(2+).The Alg-TPC-CNF composite was exhibited excellent removing efficiency which around 95%for Pb,92%for Cu,43%for Fe and 54%for Mg.These outcomes affirm that the utilization of nanomaterials giving higher adsorption capacities contrasted with similar material in its micro or macrostructure form.

Ultrasound-assisted extraction of antioxidant polyphenolic compounds from Nephelium lappaceum L.(Mexican variety) husk

Objective: To reach the recovery and identification of antioxidant polyphenolic compounds from Nephelium lappaceum L.(Mexican variety) husk using ultrasound-assisted extraction and liquid chromatography/mass spectrometry as well as the in vitro antioxidant activity. Methods: Rambutan husk extracts were obtained by ultrasound-assisted extraction, mass/volume ratio, water/ethanol percentage and extraction time were evaluated. Once the best extraction condition of polyphenolic compounds was defined, a polyphenolic fraction was recovered using Ambetlite XAD-16. The total content of antioxidant polyphenolic compounds was determined by summation of the total hydrolysable polyphenol and total condensed polyphenol contents. Recovered compounds were identified by FTIR(ATR) spectroscopy and HPLC/ESI/MS. The antioxidant activity was carried out by ABTS, DPPH and lipid oxidation inhibition in vitro methods. Results: In Mexican variety rambutan husk, the total polyphenolic content was 487.67 mg/g, after ultrasound-assisted extraction. According to the HPLC/ESI/MS analysis 12 antioxidant polyphenolic compounds were identified, mostly ellagitannins such as geraniin, corilagin and ellagic acid. The antioxidant activity determined by ABTS, DPPH and lipid oxidation inhibition methods was demonstrated. The main functional groups of the identified compounds were determined by FTIR analysis. Conclusions: It was demonstrated that ultrasound-assisted extraction was effective and allowed the extraction and recovery of antioxidant polyphenolic compounds. Furthermore Mexican variety rambutan husk is an important source for recovering polyphenolic compounds with antioxidant activity, these compounds have potential application for the treatment/prevention of various diseases related to cancer and pathogenic microorganisms.

Studies on the Synthesis of Morphinan Alkaloid:Preparation of the Key Allylic Silyl Ether Precursor

A convergent strategy to the key allylic silyl ether precursor 4 in our synthetic efforts toward morphinan alkaloid is presented. The vital step is the selective 1,2-addition of the organocerium agent of 6 to ketene 5.

The Rearrangement of 2-Benzothiazolylthioacetyl Hydrazide in Synthesis of s-Triazolo[3,4-b]benzothiazole-3-thiol

The rearrangement reaction of 2-benzothiazolylthioacetyl hydrazide 1 with potassium hydroxide and carbon disulfide in ethanol to produce s-triazolo[3, 4-b]benzothiazole-3-thiol 3 was described. 3 also can be obtained from 2-benzothiazolylhydazine 2 and the two methods for getting 3 were compared. Mannich reaction of compounds 3 was reported too.

IR Spectral Analysis of Diterpene Glycosides Isolated from <i>Stevia rebaudiana</i>

The objective is to identify the Infra-Red (IR) spectral analysis of the diterpene glycosides present in the commercial extracts of Stevia rebaudiana was achieved by PerkinElmer Spectrum 400 Fourier Transform (FT) spectrometer employing a PerkinElmer Universal Attenuated Total Reflection (ATR) accessory. Using this technique the IR spectral pattern of 15 steviol glycosides which belongs to three different classes of ent-kaurane diterpene glycosides namely ent-13-hydroxykaur-16-en-19-oic acid, ent-13-hydroxykaur-15-en-19-oic acid, and 13-methyl-16-oxo-17-norent- kauran-19-oic acid were identified. From the wave numbers found for all 15 steviol glycosides, it was observed that that though there are differences in the number of sugar units, nature of sugar units, and their attachments;there are not any notable differences in the IR values.

Molecular Modeling and Synthesis of New Heterocyclic Compounds Containing Pyrazole as Anticancer Drugs

Several modifications in CA-4 were reported in literature for the development of various tubulin inhibitors. In our study, twenty-two newly synthesized heterocyclic derivatives of Combretastatin A-4 (CA-4) have been tested for their cytotoxic effect on four different types of cells with malignant behavior using CA-4 as a positive control. Compounds 5b, 15 and 16 showed the foremost potent antiproliferative activities as compared to CA-4 with IC50 starting from 6.9 to 13.7 μM. Molecular docking was performed with the crystal structure of tubulin employing a potent tubulin inhibitor CA-4 as a parent molecule. Molecular study advised that 5b, 15, 16 and 17 are promising tubulin inhibitors.

Design, Synthesis and Cancer Cell Line Activities of Pyrazolo[3,4-<i>b</i>]pyridine Derivatives

Starting from 4,6-dimethyl-2-oxo-(1H)-3-pyridinecarbonitrile 1 and 3-aminopyrazolopyridine 4, a series of cyanopyri- dine derivatives 3a-i, Schiff bases 5a-f, urea and thiourea derivatives 6a-b, amide derivatives 7a-h, pyridopyra- zolopy-rimidine 8a-b and pyridopyrazolotriazine 10a-b were synthesized. Activities of eleven representative compounds were evaluated against A-549 (lung), HEPG2 (liver) and HCT-116 (colon) cancer cell lines. The findings revealed that some of the synthesized compounds showed remarkable anticancer activities, especially 8b which displayed the highest activity among the tested compounds with IC50 equal to 2.9, 2.6 and 2.3 μmol. In addition to synthesis and biological activities, we present discussion about the rationale of the design and activity of the potent compound 8b using struc- ture-based modeling tools.

Modelling of the Resin Penetration Rate into the Archaeological Wood Cell Wall： The Methodology of Experimental Design

The penetration modeling of an adhesive into the fiber requires the measurement of various properties of resin and fiber： the resin viscosity, its surface tension, the penetration depth and the timber pore radius. This study is based on the screening technique that identifies the factors sensed by the experimenter. In order to determine the optimum processing conditions and find the combination of parameters that maximize the productivity in the experimental phase, a geometric illustration of the response has been made. The results are： the pores radius （4 μm）, surface tension （62.5 mN/m）, depth （10 μm） and viscosity （2,000 Cp）.

Catalyst Free Synthesis of Pyridine-2,6-bis(2-bromo-propane-1,3-dione) and Pyrdine-2,6-bis(<i>N</i>-arylthiazoline-2-thiones)

We have described herein a catalyst-free preparation method of pyridine-2,6-bis(N-alkylthiazoline-2-thiones) (4a-i) by the reaction of primary amines, CS2, and pyridine-2,6-bis(2-bromo-1,3- dicarbonyl) derivatives (2a-c) in water. Also, we have described a catalyst free, green chemistry protocols to monobromination of pyridine-2,6-bis(2-bromo-1,3-dicarbonyl) derivatives with high yield, using NBS as a brominating agent, that led to eco-friendly isolation and purification proce-dures. Furthermore, we have studied the reactivity of pyridine-2,6-bis(2-bromo-1-methyl-pro- pane-1,3-dione) (2a) towards thiourea to afford 2,6-bis(5-benzoyl-2-aminothiazol-4-yl)pyridine (9).

Interaction between N-phosphoryl-α-,β-and γ-amino acids and nucleosides

The reactions of four different N-（O,O＇-diisopropyl） phosphoamino acids （DIPP-aa）, such as N-phosphoryl-L-α-alanine （DIPP- L-α-Ala）, N-phosphoryl-D-α-alanine （DIPP-D-α-A1a）, N-phosphoryl-β-alanine （DIPP-β-A1a） and N-phosphoryl-γ-amino butyric acid （DIPP-γ-Aba）, and four nucleosides, adenosine （A）, guanosine （G）, cytidine （C） and uridine （U）, were studied by electrospray ionization tandem mass spectrometry （ESI-MS/MS） and HPLC/ESI-MS. DIPP-L-α-A1a and DIPP-D-α-A1a produced the same phosphorylated nucleosides, dinucleotides and phosphoroligopeptide. However, DIPP-β-A1a and DIPP-γ-Aba gave no relevant products.

Preparation and Characterization of Alkyd Resins Based on Citrullus colocynthis Seed Oil

In this study,different samples of alkyd resins based on Citrullus colocynthis seed oil(CCSO)—which has a high content of linoleic acid—were prepared as a renewable raw material.Short(I),medium(II),and long(III)alkyd resins were synthesized using oil,glycerol,and phthalic anhydride(PA)in different proportions.Prunus mahaleb seed oil(PMSO),which contains conjugated linolenic acid,was blended with CCSO in different proportions to examine the effect of PMSO on the film properties of alkyd resins(IV and V).All synthesized resins were characterized by FTIR and 1H NMR spectroscopic analysis.These resins were also cured by an epoxy resin and their film properties(pencil hardness,adhesion,gloss,and chemical resistance)were determined.Analysis of these alkyds reveals that CCSO can be used as a new potential raw material for coating applications.