Mass spectrometry in structural and stereochemical problems. Part CLIII. Electron impact-promoted fragmentation of n-alkyl cyanides

In spite of previous extensive studies on the mass spectrometry of alkyl cyanides, no good mechanistic insight has as yet been gained into the behavior of straight chain alky1 cyanides. For this reason the possible origins for the principal ions in the mass spectrum of a typical alkyl cyanide (n-hexyl cyanide) have been determined using high resolution mass spectrometry anddeuterium labeling of every carbon atom. The results lead to the conclusion that most of the typical fragmentation processes of n-alkyl cyanides proceed through cyclic intermediates.     

Reaction of Pyrimidinonethione Derivatives: Synthesis of N‐Methyl‐2‐Hydrizinopyrimidine‐4‐One,Thiazolo[3,4‐b] N‐Methylpyrimidinone; 2‐(1‐Pyrazolonyl) N‐Methylpyrimidine‐4‐one and 2‐Hydrazino‐N‐Methyl Pyrimidine‐4‐One Derivatives

6‐Aryl‐5‐cyano‐4‐pyrimidinone‐2‐thion derivatives 1a‐c reacted with methyl iodide (1:2) to give the corresponding 2‐S,N‐dimethyl pyrimidine‐4‐one derivatives 2a‐c . Compounds 2a‐c were in turn, reacted with hydrazine hydrate to give the sulfur free reaction products 3a‐c . These reaction products were taken as the starting materials for the synthesis of several new heterocyclic derivatives. Reaction of 3a‐c with acetic anhydride and formic acid gave pyrimido triazines 4a‐c and 7a‐c , respectively. Their reactions with active methylene containing reagents gave the corresponding 2‐(1‐pyrazonyl)‐N‐methyl pyrimidine derivatives 9a‐c and 10a‐c , respectively. Their reactions with aromatic aldehydes afforded the corresponding 2‐hydrazono pyrimidine derivatives 11a‐c . The structure of these reactions products were established based on both elemental analysis and spectral data studies.     

A novel ion selective membrane potentiometric sensor for direct determination of Fe(III) in the presence of Fe(II)

A new PVC membrane potentiometric sensor that is highly selective to Fe(III) ions was prepared by using 2-[(2-hydroxy-1-propenyl-buta-1,3-dienylimino)-methyl]-4-p-tolylazo-phenol [HPDTP] as a suitable carrier. The electrode exhibits a linear response for iron(III) ions over a wide concentration range (3.5 × 10⁻⁶ to 4.0 × 10⁻²) with a super Nernstian slope of 28.5 (±0.5) per decade. The electrode can be used in the pH range from 4.5 to 6.5. The proposed sensor shows fairly a good discriminating ability towards Fe³⁺ ion in comparison to some hard and soft metals such as Fe²⁺, Cd²⁺, Cu²⁺, Al³⁺ and Ca²⁺. It has a response time of <15 s and can be used for at least 2 months without any measurable divergence in response characteristics. The electrode was used in the direct determination of Fe³⁺ in aqueous samples and as an indicator electrode in potentiometric titration of Fe(III) ions.     

Synthesis and Reactions of Some New Heterocyclic Compounds Containing Cycloalka[e]thieno[2,3‐b]pyridine Moiety

Hydrolysis of ethyl 3-amino-4-aryl-cycloalka[e]thieno[2,3-b]pyridine-2-carboxylates ( 3a-d) gave the corresponding o-aminocarboxylic acids 4a-d . Heating the latter compounds ( 4a-d) with acetic anhydride furnished the oxazinone derivatives 5a-d which, in turn, underwent recyclization reaction to give the corresponding pyrimidinones 6a-d upon treatment with ammonium acetate in acetic acid. Reaction of 3-amino-4-aryl-cycloalka[e]thieno[2,3-b]pyridine-2-carboxamides ( 3f,h ) with triethyl orthoformate gave pyrimidinone derivatives 7a,b . Reaction of 3-amino-4-phenyl-cycloalka[e]thieno[2,3-b]pyridine-2-carboxamides 3e,h with aromatic aldehydes furnished tetrahydropyridothienopyrimidinones 8a-d . Chlorination of 7a,b and 6a-d by using phosphorous oxychloride produced 4-chlorocycloalka[5′,6′]pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidine derivatives 9a-f which were used as key intermediates in the synthesis of several new cycloalkapyrido-thienopyrimidines 10a-f ˜ 14a-f . Moreover, some cycloalkapyridothienotriazinones 15a,b-17a,b were synthesized.     

The effect of block copolymer structure on the internalization of polymeric micelles by human breast cancer cells

The objective of this study was to assess the effect of hydrophilic/hydrophobic block chain lengths on the internalization of poly(ethylene oxide)-block-poly(varepsilon-caprolactone) (PEO-b-PCL) micelles by cancer cells. PEO-b-PCL block copolymers with varied PEO and PCL chain lengths were synthesized, assembled to polymeric micelles and loaded with a hydrophobic fluorescent probe (DiI) through a co-solvent evaporation method of physical encapsulation. The slow release of the fluorescent probe from the micellar structure was evidenced following DiI transfer to lipid vesicles. The extent of micellar uptake by cancer cells was investigated through their incubation with MCF-7 cells followed by measurement of the fluorescent emission intensity of DiI (lambda=550 nm) in separated lysed cells. Cellular internalization of polymeric micelles was confirmed by laser scanning microscopy. The mechanism of micellar uptake was investigated by pretreatment of MCF-7 cells with chlorpromazine and cytochalasin B. Encapsulation of DiI in PEO-b-PCL micelles lowered the extent and rate of hydrophobic probe internalization by cancer cells. For polymeric micelles with 5000 gmol(-1) of PCL and varied PEO molecular weights of 2000, 5000 and 13,000 gmol(-1), maximum uptake was observed at a PEO molecular weight of 5000 gmol(-1). For polymeric micelles with 5000 gmol(-1) of PEO and varied PCL molecular weights of 5000, 13,000 and 24,000 gmol(-1), maximum uptake was observed at 13,000 gmol(-1) of PCL. Chlorpromazine reduced the cellular uptake of PEO-b-PCL micelles independent from the block copolymer structure, pointing to the involvement of clathrin mediated endocytosis mechanisms in the uptake of polymeric micelles by cancer cells. Inhibition of cellular uptake of PEO-b-PCL micelles by cytochalasin B, on the other hand, was found to be dependent on the chemical structure of the core/shell forming blocks.     

Radiolysis of iodotyrosines in aqueous-ethanol solutions

⁶⁰Co-gamma radiolysis of 3-iodotyrosine and 3,5-diiodotyrosine in aqueous-ethanol solutions has shown that the chemical effects are mainly determined by the interaction of radicals from the radiolysis of solvent and controlled by the composition of the solution. The influence of varying solvent composition and radiation dose on the amount of iodoamino acid converted and on the yields of the radiolysis products (I₂, I^–, IO ₃ ^– and H₂O₂) formed in aerated solutions at room termperature were investigated. The formation of I₂ is dependent upon the acidity of the solution and is mainly produced as an after-effect due to the interaction of H₂O₂ with I^– ions, both being radiolysis products. The variation of radiation-chemical yields with the solute and solvent composition, and the probable mechanisms for formation of the radiolysis products are discussed.     

Chemical Markers and Pharmacological Characters of Pelargonium graveolens Essential Oil from Palestine

Pelargonium graveolens leaves are widely used in traditional medicine for relieving some cardiovascular, dental, gastrointestinal, and respiratory disorders. They are also used as food and tea additives in Palestine and many other countries. Consequently, this investigation aimed to describe the chemical markers, cytotoxic, antioxidant, antimicrobial, metabolic, and cyclooxygenase (COX) enzymes inhibitory characteristics of P. graveolens essential oil (PGEO) from Palestine utilizing reference methods. There were 70 chemicals found in the GCMS analysis, and oxygenated terpenoids were the most abundant group of the total PGEO. Citronellol (24.44%), citronellyl formate (15.63%), γ-eudesmol (7.60%), and iso-menthone (7.66%) were the dominant chemical markers. The EO displayed strong antioxidant activity (IC₅₀ = 3.88 ± 0.45 µg/mL) and weak lipase and α-amylase suppressant effects. Notably, the PGEO displayed high α-glucosidase inhibitory efficacy compared with Acarbose, with IC₅₀ doses of 52.44 ± 0.29 and 37.15 ± 0.33 µg/mL, respectively. PGEO remarkably repressed the growth of methicillin-resistant Staphylococcus aureus (MRSA), even more than Ampicillin and Ciprofloxacin, and strongly inhibited Candida albicans compared with Fluconazole. The highest cytotoxic effect of the PGEO was noticed against MCF-7, followed by Hep3B and HeLa cancer cells, with IC₅₀ doses of 32.71 ± 1.25, 40.71 ± 1.89, and 315.19 ± 20.5 µg/mL, respectively, compared with doxorubicin. Moreover, the screened EO demonstrated selective inhibitory activity against COX-1 (IC₅₀ = 14.03 µg/mL). Additionally, PGEO showed a weak suppressant effect on COX-2 (IC₅₀ = 275.97 µg/mL). The current research can be considered the most comprehensive investigation of the chemical and pharmacological characterization of the PGEO. The results obtained in this study demonstrate, without doubt, that this plant represents a rich source of bioactive substances that can be further investigated and authenticated for their medicinal potential.     

Natural Small Molecules in Gastrointestinal Tract and Associated Cancers: Molecular Insights and Targeted Therapies

Gastric cancer is one of the most common cancers of the gastrointestinal tract. Although surgery is the primary treatment, serious maladies that dissipate to other parts of the body may require chemotherapy. As there is no effective procedure to treat stomach cancer, natural small molecules are a current focus of research interest for the development of better therapeutics. Chemotherapy is usually used as a last resort for people with advanced stomach cancer. Anti-colon cancer chemotherapy has become increasingly effective due to drug resistance and sensitivity across a wide spectrum of drugs. Naturally-occurring substances have been widely acknowledged as an important project for discovering innovative medications, and many therapeutic pharmaceuticals are made from natural small molecules. Although the beneficial effects of natural products are as yet unknown, emerging data suggest that several natural small molecules could suppress the progression of stomach cancer. Therefore, the underlying mechanism of natural small molecules for pathways that are directly involved in the pathogenesis of cancerous diseases is reviewed in this article. Chemotherapy and molecularly-targeted drugs can provide hope to colon cancer patients. New discoveries could help in the fight against cancer, and future stomach cancer therapies will probably include molecularly formulated drugs.     

Iridoids Isolation from a Phytochemical Study of the Medicinal Plant Teucrium parviflorum Collected in Iraqi Kurdistan

Herbal medicines are still widely practiced in Kurdistan Region-Iraq, especially by people living in villages on mountainous regions. Among plants belonging to the genus Teucrium (family Lamiaceae), which are commonly employed in the Kurdish traditional medicine, we have analyzed, for the first time, the methanol and aqueous methanol extracts of T. parviflorum aerial parts. The plant is mainly used by Kurds to treat jaundice, liver disorders and stomachache. We aimed to determine the phytochemical profile of the extracts and the structures of the main components, so to provide a scientific rationale for the ancient use of the plant in the ethno-pharmacological field. TLC analysis of the two extracts on silica gel and reversed phase TLC plates, using different visualization systems, indicated similar contents and the presence of phenolics, flavonoids, terpenoids and sugars. The chlorophyll-free extracts exhibited weak/no antimicrobial activities against a panel of bacteria (MICs = 800–1600 µg/mL) and fungal strains (MICs ≥ 5 mg/mL). At the concentration of 600 µg/mL, the methanol extract showed moderate antiproliferative effects against A549 and MCF-7 cancer cell lines in the MTS assay. Moreover, both extracts exhibited a significant dose-dependent free radical scavenging action against the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical (EC₅₀ = 62.11 and 44.25 μg/mL, respectively). In a phytochemical study, a high phenolic content (77.08 and 81.47 mg GAE/g dry extract, respectively) was found in both extracts by the Folin–Ciocalteu assay. Medium pressure liquid chromatographic (MPLC) separation of the methanol extract on a reversed phase cartridge eluted with a gradient of MeOH in H₂O, afforded two bioactive iridoid glucosides, harpagide (1) and 8-O-acetylharpagide (2). The structures of 1 and 2 were established by spectral data, chemical reactions, and comparison with the literature. Interestingly, significant amounts of hepatotoxic furano neo-clerodane diterpenoids, commonly occurring in Teucrium species, were not detected in the extract. The wide range of biological activities reported in the literature for compounds 1 and 2 and the significant antiradical effects of the extracts give scientific support to the traditional use in Iraqi Kurdistan of T. parviflorum aerial parts for the preparation of herbal remedies.     

Determination of Chemical Compounds and Investigation of Biological Properties of Matricaria chamomilla Essential Oils,Honey, and Their Mixture

This exploratory investigation aimed to determine the chemical composition and evaluate some biological properties, such as antioxidant, anti-inflammatory, antidiabetic, and antimicrobial activities, of Matricaria chamomilla L. essential oils (EOs). EOs of M. chamomilla were obtained by hydrodistillation and phytochemical screening was performed by gas chromatography–mass spectrophotometry (GC-MS). The antimicrobial activities were tested against different pathogenic strains of microorganisms by using disc diffusion assay, the minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) methods. The antidiabetic activity was performed in vitro using the enzyme inhibition test. The antioxidant activity of EOs was tested using the free radical scavenging ability (DPPH method), ferrous ion chelating (FIC) ability, and β-carotene bleaching assay. The anti-inflammatory effects were tested in vivo using the carrageenan-induced paw edema method and in vitro using the inhibition of the lipoxygenase test. The analysis of the phytochemical composition by GC-MS revealed that camphor (16.42%) was the major compound of EOs, followed by 3-carene (9.95%), β-myrcene (8.01%), and chamazulene (6.54%). MCEO, honey, and their mixture exhibited antioxidant activity against the DPPH assay (IC₅₀ ranging from 533.89 ± 15.05 µg/mL to 1945.38 ± 12.71 µg/mL). The mixture exhibited the best radical scavenging activity, with an IC₅₀ of 533.89 ± 15.05 µg/mL. As antidiabetic effect, EO presented the best values against α-glucosidase (265.57 ± 0.03 μg/mL) and α-amylase (121.44 ± 0.05 μg/mL). The EOs and honey mixture at a dose of 100 mg/kg exhibited a high anti-inflammatory effect, with 63.75% edema inhibition after 3 h. The impact of EOs on the studied species showed an excellent antimicrobial (Staphylococcus aureus ATCC 29213 (22.97 ± 0.16 mm)), antifungal (Aspergillus niger (18.13 ± 0.18 mm)) and anti-yeast (Candida albicans (21.07 ± 0.24 mm) effect against all the tested strains. The results obtained indicate that the EOs of M. chamomilla could be a potential drug target against diabetes, inflammation and microbial infections; however, further investigations to assess their bioactive molecules individually and in combination are greatly required.