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.     

Efficient Oxidation of Cyclohexane over Bulk Nickel Oxide under Mild Conditions

Nickel oxide powder was prepared by simple calcination of nickel nitrate hexahydrate at 500 °C for 5 h and used as a catalyst for the oxidation of cyclohexane to produce the cyclohexanone and cyclohexanol—KA oil. Molecular oxygen (O₂), hydrogen peroxide (H₂O₂), t-butyl hydrogen peroxide (TBHP) and meta-chloroperoxybenzoic acid (m-CPBA) were evaluated as oxidizing agents under different conditions. m-CPBA exhibited higher catalytic activity compared to other oxidants. Using 1.5 equivalent of m-CPBA as an oxygen donor agent for 24 h at 70 °C, in acetonitrile as a solvent, NiO powder showed exceptional catalytic activity for the oxidation of cyclohexane to produce KA oil. Compared to different catalytic systems reported in the literature, for the first time, about 85% of cyclohexane was converted to products, with 99% KA oil selectivity, including around 87% and 13% selectivity toward cyclohexanone and cyclohexanol, respectively. The reusability of NiO catalyst was also investigated. During four successive cycles, the conversion of cyclohexane and the selectivity toward cyclohexanone were decreased progressively to 63% and 60%, respectively, while the selectivity toward cyclohexanol was increased gradually to 40%.     

Carnosic Acid Encapsulated in Albumin Nanoparticles Induces Apoptosis in Breast and Colorectal Cancer Cells

Carnosic acid (CA) is a natural phenolic compound with several biomedical actions. This work was performed to study the use of CA-loaded polymeric nanoparticles to improve the antitumor activity of breast cancer cells (MCF-7) and colon cancer cells (Caco-2). CA was encapsulated in bovine serum albumin (BSA), chitosan (CH), and cellulose (CL) nanoparticles. The CA-loaded BSA nanoparticles (CA-BSA-NPs) revealed the most promising formula as it showed good loading capacity and the best release rate profile as the drug reached 80% after 10 h. The physicochemical characterization of the CA-BSA-NPs and empty carrier (BSA-NPs) was performed by the particle size distribution analysis, transmission electron microscopy (TEM), and zeta potential. The antitumor activity of the CA-BSA-NPs was evaluated by measuring cell viability, apoptosis rate, and gene expression of GCLC, COX-2, and BCL-2 in MCF-7 and Caco-2. The cytotoxicity assay (MTT) showed elevated antitumor activity of CA-BSA-NPs against MCF-7 and Caco-2 compared to free CA and BSA-NPs. Moreover, apoptosis test data showed an arrest of the Caco-2 cells at G₂/M (10.84%) and the MCF-7 cells at G2/M (4.73%) in the CA-BSA-NPs treatment. RT-PCR-based gene expression analysis showed an upregulation of the GCLC gene and downregulation of the BCL-2 and COX-2 genes in cells treated with CA-BSA-NPs compared to untreated cells. In conclusion, CA-BSA-NPs has been introduced as a promising formula for treating breast and colorectal cancer.     

Ziziphus nummularia: A Comprehensive Review of Its Phytochemical Constituents and Pharmacological Properties

Ziziphus nummularia, a small bush of the Rhamnaceae family, has been widely used in traditional folk medicine, is rich in bioactive molecules, and has many reported pharmacological and therapeutic properties. Objective: To gather the current knowledge related to the medicinal characteristics of Z. nummularia. Specifically, its phytochemical contents and pharmacological activities in the treatment of various diseases such as cancer, diabetes, and cardiovascular diseases, are discussed. Methods: Major scientific literature databases, including PubMed, Scopus, ScienceDirect, SciFinder, Chemical Abstracts, Medicinal and Aromatic Plants Abstracts, Henriette’s Herbal Homepage, Dr. Duke’s Phytochemical and Ethnobotanical Databases, were searched to retrieve articles related to the review subject. General web searches using Google and Google scholar were also utilized. The search period covered articles published between 1980 and the end of October 2021.The search used the keywords ‘Ziziphus nummularia’, AND (‘phytochemical content’, ‘pharmacological properties, or activities, or effects, or roles’, ‘anti-inflammatory’, ‘anti-drought’, ‘anti-thermal’, ‘anthelmintic’, ‘antidiabetic’,’ anticancer’, ‘anticholinesterase’, ‘antimicrobial’, ‘sedative’, ‘antipyretic’, ‘analgesic’, or ‘gastrointestinal’). Results: This plant is rich in characteristic alkaloids, especially cyclopeptide alkaloids such as nummularine-M. Other phytochemicals, including flavonoids, saponins, glycosides, tannins, and phenolic compounds, are also present. These phytochemicals are responsible for the reported pharmacological properties of Z. nummularia, including anti-inflammatory, antioxidant, antimicrobial, anthelmintic, antidiabetic, anticancer, analgesic, and gastrointestinal activities. In addition, Z. nummularia has anti-drought and anti-thermal characteristics. Conclusion: Research into the phytochemical and pharmacological properties of Z. nummularia has demonstrated that this plant is a rich source of novel bioactive compounds. So far, Z. nummularia has shown a varied pharmacological profile (antioxidant, anticancer, anti-inflammatory, and cardioprotective), warranting further research to uncover the therapeutic potential of the bioactives of this plant. Taken together, Z. nummularia may represent a new potential target for the discovery of new drug leads.     

Novel Design of RNA Aptamers as Cancer Inhibitors and Diagnosis Targeting the Tyrosine Kinase Domain of the NT-3 Growth Factor Receptor Using a Computational Sequence-Based Approach

Aptamers, the nucleic acid analogs of antibodies, bind to their target molecules with remarkable specificity and sensitivity, making them promising diagnostic and therapeutic tools. The systematic evolution of ligands by exponential enrichment (SELEX) is time-consuming and expensive. However, regardless of those issues, it is the most used in vitro method for selecting aptamers. Therefore, recent studies have used computational approaches to reduce the time and cost associated with the synthesis and selection of aptamers. In an effort to present the potential of computational techniques in aptamer selection, a simple sequence-based method was used to design a 69-nucleotide long aptamer (mod_09) with a relatively stable structure (with a minimum free energy of −32.2 kcal/mol) and investigate its binding properties to the tyrosine kinase domain of the NT-3 growth factor receptor, for the first time, by employing computational modeling and docking tools.     

Time‐Varying Flexible Least Squares for Thermal Desorption of Gases

Time‐varying linear regression via flexible least squares is used to determine temperature‐dependent kinetic parameters during low‐pressure, steady‐state, temperature‐programmed desorption from catalytic surfaces. The flexible least squares approach optimizes time‐varying parameters by minimizing dynamic and measurement discrepancies between a linear theoretical model and experimental data using linear regression. The effectiveness of this approach is demonstrated by calculation of accurate temperature‐dependent activation energies, preexponential factors, and differential conversion functions for the evolution of 3‐methyl‐2‐oxetanone (β‐lactone) during the selective oxidation of isobutane over aluminum phosphomolybdates.     

Silver(I)‐N‐heterocyclic carbene complexes of bis‐imidazol‐2‐ylidenes having different aromatic‐spacers: synthesis,crystal structure,and in vitro antimicrobial and anticancer studies

A series of Ag(I) complexes ( 6 , 7 , 8 , 9 ) derived from imidazol‐2‐ylidenes was synthesized by reacting Ag₂O with an o‐, m‐, p‐xylyl or 1,3,5‐triazine‐linked imidazolium salts ( 1 , 2 , 3 , 4 ) and then characterizing these using various spectro‐analytical techniques. Additionally, triazine‐linked bis‐imidazolium salt 5 was characterized using the single‐crystal X‐ray diffraction method. Complexes 6–9 were formed from the N‐heterocyclic carbene ligand precursors 1–3 as PF₆^‐ salts in good yields. Conversely, salt 5 does not form Ag(I) complex even under various reaction conditions. Using ampicillin as a standard, complexes 6–9 were tested against bacteria strains Escherichia coli and Staphylococcus aureus as Gram‐negative and Gram‐positive bacteria, respectively, showing potent antimicrobial activities against the tested bacteria even at minimum inhibition concentration and bacterial concentration levels. Furthermore, the potential anticancer activities of the reported complexes were evaluated against the human colorectal cancer (HCT 116) cell lines, using 5‐fluorouracil as a standard drug. The highest anticancer activities were observed for complex 8 with an IC₅₀ value of 3.4 μm , whereas the lowest was observed for complex 9 with an IC₅₀ value of 18.1 μm . Copyright © 2013 John Wiley & Sons, Ltd.