1,3,4-Oxadiazole N-Mannich Bases: Synthesis,Antimicrobial, and Anti-Proliferative Activities

The reaction of 5-(3,4-dimethoxyphenyl)-1,3,4-oxadiazole-2(3H)-thione 3 with formaldehyde solution and primary aromatic amines or 1-substituted piperazines, in ethanol at room temperature yielded the corresponding N-Mannich bases 3-arylaminomethyl-5-(3,4-dimethoxyphenyl)-1,3,4-oxadiazole-2(3H)-thiones 4a–l or 3-[(4-substituted piperazin-1-yl)methyl]-5-(3,4-dimethoxyphenyl)-1,3,4-oxadiazole-2(3H)-thiones 5a–d, respectively. The in vitro inhibitory activity of compounds 4a–l and 5a–d was assessed against pathogenic Gram-positive, Gram-negative bacteria, and the yeast-like pathogenic fungus Candida albicans. The piperazinomethyl derivatives 5c and 5d displayed broad-spectrum antibacterial activities the minimal inhibitory concentration (MIC) 0.5–8 μg/mL) and compounds 4j, 4l, 5a, and 5b showed potent activity against the tested Gram-positive bacteria. In addition, the anti-proliferative activity of the compounds was evaluated against prostate cancer (PC3), human colorectal cancer (HCT-116), human hepatocellular carcinoma (HePG-2), human epithelioid carcinoma (HeLa), and human breast cancer (MCF7) cell lines. The optimum anti-proliferative activity was attained by compounds 4l, 5a, 5c, and 5d.     

Removal of Cd(II), Cu(II), and Pb(II) by adsorption onto natural clay: a kinetic and thermodynamic study

In this work, we study the elimination of three bivalent metal ions (Cd²⁺, Cu²⁺, and Pb²⁺) by adsorption onto natural illitic clay (AM) collected from Marrakech region in Morocco. The characterization of the adsorbent was carried out by X-ray fluorescence, Fourier transform infrared spectroscopy and X-ray diffraction. The influence of physicochemical parameters on the clay adsorption capacity for ions Cd²⁺, Cu²⁺, and Pb²⁺, namely the adsorbent dose, the contact time, the initial pH imposed on the aqueous solution, the initial concentration of the metal solution and the temperature, was studied. The adsorption process is evaluated by different kinetic models such as the pseudo-first-order, pseudo-second-order, and Elovich. The adsorption mechanism was determined by the use of adsorption isotherms such as Langmuir, Freundlich, and Temkin models. Experiments have shown that heavy metals adsorption kinetics onto clay follows the same order, the pseudo-second order. The isotherms of adsorption of metal cations by AM clay are satisfactorily described by the Langmuir model and the maximum adsorption capacities obtained from the natural clay, using the Langmuir isotherm model equation, are 5.25, 13.41, and 15.90 mg/g, respectively for Cd(II), Cu(II), and Pb(II) ions. Adsorption of heavy metals on clay is a spontaneous and endothermic process characterized by a disorder of the medium. The values of ΔH are greater than 40 kJ/mol, which means that the interactions between clay and heavy metals are chemical in nature.     

Uranium concentration measurements in human blood for some governorates in Iraq using CR-39 track detector

The sensitive and simple technique of fission track etch has been applied to determine trace concentration of uranium in blood samples for occupational and non-occupational workers, male and female, using CR-39 track detector that is employed for registration of induced fission tracks. The results show that the highest recorded uranium concentration in human blood of workers in the ministry of Science and Technology were 1.90 ppb (male, 36 years old, 12 years' work experience, and living in Basrah governorate) and minimum concentration 0.26 ppb (female, 40 years old, 10 years' work experience, and living in Baghdad), while for non-occupational worker, the maximum uranium concentration was 1.76 ppb (female, 63 years old, and living in Al-Muthana) and minimum concentration was 0.28 ppb (female, 20 years old, and living in Baghdad). It has also been found that the uranium concentration in human blood samples of workers in the ministry of Science and Technology are higher than those of non-occupational workers, and the uranium concentrations for female workers and for non-occupational workers were higher than those for male workers and non-occupational workers.     

Structural Insights and Docking Analysis of Adamantane-Linked 1,2,4-Triazole Derivatives as Potential 11β-HSD1 Inhibitors

The solid-state structural analysis and docking studies of three adamantane-linked 1,2,4-triazole derivatives are presented. Crystal structure analyses revealed that compound 2 crystallizes in the triclinic P-1 space group, while compounds 1 and 3 crystallize in the same monoclinic P2₁/c space group. Since the only difference between them is the para substitution on the aryl group, the electronic nature of these NO₂ and halogen groups seems to have no influence over the formation of the solid. However, a probable correlation with the size of the groups is not discarded due to the similar intermolecular disposition between the NO₂/Cl substituted molecules. Despite the similarities, CE-B3LYP energy model calculations show that pairwise interaction energies vary between them, and therefore the total packing energy is affected. HOMO-LUMO calculated energies show that the NO₂ group influences the reactivity properties characterizing the molecule as soft and with the best disposition to accept electrons. Further, in silico studies predicted that the compounds might be able to inhibit the 11β-HSD1 enzyme, which is implicated in obesity and diabetes. Self- and cross-docking experiments revealed that a number of non-native 11β-HSD1 inhibitors were able to accurately dock within the 11β-HSD1 X-ray structure 4C7J. The molecular docking of the adamantane-linked 1,2,4-triazoles have similar predicted binding affinity scores compared to the 4C7J native ligand 4YQ. However, they were unable to form interactions with key active site residues. Based on these docking results, a series of potentially improved compounds were designed using computer aided drug design tools. The docking results of the new compounds showed similar predicted 11β-HSD1 binding affinity scores as well as interactions to a known potent 11β-HSD1 inhibitor.     

Dyeing wool and cotton fibres with acidic extract of Hibiscus rosa sinensis flower

Abstract

The focus of this work is to extract a natural dye for colouring camel wool as a substitute for synthetic dyes used in the Sadu House of Kuwait. Their target is to keep the tradition of tent and rug production natural in all its manifestations. Therefore, our task was to find an abundant source that provides a colour preferably red to purple. Hibiscus rosa sinensis (HRS) is an abundantly available plant in Kuwait that was explored for extraction of the red dye to colour camel wool permanently. The powdered petals of red flowers of HRS was extracted with 5% acetic acid which yielded a deep red colour that showed a great potential for woollen fibre dyeing. The use of mordants like alum and some metal salts manifested a wide range of fixed colours which intensified at 85 °C. The colours produced had excellent fastness and was accepted by the Sadu House.     

Synthesis and Crystal Structure of a New Mixed Alkali Oxalate A1?x(NH4)x(H2C2O4)(HC2O4)(H2O)2 with A?=?K, Rb

Abstract  

In the present study we report the synthesis, crystal structure, spectroscopic and thermal analysis of mixed alkali A_1−x (NH₄) _x (H₂C₂O₄)(HC₂O₄)(H₂O)₂ with A = K, Rb. Single crystal refinements showed that the two compounds Rb_0.86(NH₄)_0.14(H₂C₂O₄)(HC₂O₄)(H₂O)₂ and K_0.53(NH₄)_0.47(H₂C₂O₄)(HC₂O₄)(H₂O)₂ adopt P − 1 space group. The nine fold coordination cationic sites are randomly occupied by Rb⁺/NH₄ ⁺ and K⁺/NH₄ ⁺ respectively for rubidium and potassium compounds. The structure consists of a three-dimensional network formed by the succession along (c) axis of corrugated sheets formed by alkali polyhedra layers in the packing of four-membered rings [A₄(HC₂O₄)₂(H₂C₂O₄)₂] linked and bridged by oxalate groups that behave as bi and tetradentate ligand under three different coordination modes. The stability of the crystal lattice is ensured by interesting hydrogen bonding contacts: N–H···O and O–H···O. The thermal behavior under air reveals two anomalies at 368 and 402 K attributed respectively to a structural phase transition probably due to the reorientation of ammonium tetrahedral and to the release of crystalline water. IR spectroscopy further confirms that this material loses crystallization water gradually in the temperature range 400–460 K.     

Doxorubicin-Conjugated Zinc Oxide Nanoparticles,Biogenically Synthesised Using a Fungus Aspergillus niger,Exhibit High Therapeutic Efficacy against Lung Cancer Cells

This study reports the therapeutic effectiveness of doxorubicin-conjugated zinc oxide nanoparticles against lung cancer cell line. The zinc oxide nanoparticles (ZnONPs) were first synthesised using a fungus, isolated from air with an extraordinary capability to survive in very high concentrations of zinc salt. Molecular analysis based on 18S rRNA gene sequencing led to its identification as Aspergillus niger with the NCBI accession no. {"type":"entrez-nucleotide","attrs":{"text":"OL636020","term_id":"2155690654"}}OL636020. The fungus was found to produce ZnONPs via the reduction of zinc ions from zinc sulphate. The ZnONPs were characterised by various biophysical techniques. ZnONPs were further bioconjugated with the anti-cancer drug doxorubicin (DOX), which was further confirmed by different physical techniques. Furthermore, we examined the cytotoxic efficacy of Doxorubicin-bioconjugated-ZnONPs (DOX-ZnONPs) against lung cancer A549 cells in comparison to ZnONPs and DOX alone. The cytotoxicity caused due to ZnONPs, DOX and DOX-ZnONPs in lung cancer A549 cells was assessed by MTT assay. DOX-ZnONPs strongly inhibited the proliferation of A549 with IC50 value of 0.34 μg/mL, which is lower than IC50 of DOX alone (0.56 μg/mL). Moreover, DOX-ZnONPs treated cells also showed increased nuclear condensation, enhanced ROS generation in cytosol and reduced mitochondrial membrane potential. To investigate the induction of apoptosis, caspase-3 activity was measured in all the treated groups. Conclusively, results of our study have established that DOX-ZnONPs have strong therapeutic efficacy to inhibit the growth of lung cancer cells in comparison to DOX alone. Our study also offers substantial evidence for the biogenically synthesised zinc oxide nanoparticle as a promising candidate for a drug delivery system.     

Design,Synthesis, Biological Evaluation,and Computational Studies of Novel Tri-Aryl Imidazole-Benzene Sulfonamide Hybrids as Promising Selective Carbonic Anhydrase IX and XII Inhibitors

A novel series of tri-aryl imidazole derivatives 5a–n carrying benzene sulfonamide moiety has been designed for their selective inhibitory against hCA IX and XII activity. Six compounds were found to be potent and selective CA IX inhibitors with the order of 5g > 5b > 5d > 5e > 5g > 5n (Ki = 0.3–1.3 μM, and selectivity ratio for hCA IX over hCA XII = 5–12) relative to acetazolamide (Ki = 0.03 μM, and selectivity ratio for hCA IX over hCA XII = 0.20). The previous sixth inhibitors have been further investigated for their anti-proliferative activity against four different cancer cell lines using MTT assay. Compounds 5g and 5b demonstrated higher antiproliferative activity than other tested compounds (with GI₅₀ = 2.3 and 2.8 M, respectively) in comparison to doxorubicin (GI₅₀ = 1.1 M). Docking studies of these two compounds adopted orientation and binding interactions with a higher liability to enter the active side pocket CA-IX selectively similar to that of ligand 9FK. Molecular modelling simulation showed good agreement with the acquired biological evaluation.