An Optimization Study of Cobalt Supported on Activated Carbon for the Catalytic Ozonation of Oxalic Acid: Effect of Operating Parameters and Synergetic Combination

In this study, new heterogeneous cobalt (Co) catalysts supported on activated carbon (Co/AC) were developed using a wetness impregnation process. The effect of preparation conditions on catalyst characteristics was examined. This work focused on two key parameters: the impregnation rate and the calcination atmosphere (temperature and time). Different catalysts were prepared by varying the Co loading on AC. Various catalysts were characterized by means of nitrogen sorptiometry at 77K, Boehm and pHpzc analysis. It was found that the catalyst properties and the functional surface groups were affected by the operating conditions. The best surface area was 997.5 m2/g obtained when the activated carbon was impregnated with 5% Co loading and calcined at 350°C for 2 h. The effects of parameters, such as cobalt loading, pH, catalyst dose, and ozone dose, were explored on oxalic acid removal (OA). Results show that the use of Co/AC for heterogeneous catalytic ozonation enhanced the degradation efficiency of oxalic acid (OA) significantly compared with simple ozonation and O3/AC. The main results indicate that the optimum catalytic activity was observed when 5% (wt/wt) of Co was supported on AC reaching a catalytic ozonation efficiency of 95%. The results of total organic carbon removal of 91% were achieved at optimum conditions.     

Halting Tumor Progression via Novel Non-Hydroxamate Triazole-Based Mannich Bases MMP-2/9 Inhibitors; Design,Microwave-Assisted Synthesis,and Biological Evaluation

Matrix metalloproteinases (MMPs) are key signaling modulators in the tumor microenvironment. Among MMPs, MMP-2 and MMP-9 are receiving renewed interest as validated druggable targets for halting different tumor progression events. Over the last decades, a diverse range of MMP-2/9 inhibitors has been identified starting from the early hydroxamic acid-based peptidomimetics to the next generation non-hydroxamates. Herein, focused 1,2,4-triazole-1,2,3-triazole molecular hybrids with varying lengths and decorations, mimicking the thematic features of non-hydroxamate inhibitors, were designed and synthesized using efficient protocols and were alkylated with pharmacophoric amines to develop new Mannich bases. After full spectroscopic characterization the newly synthesized triazoles tethering Mannich bases were subjected to safety assessment via MTT assay against normal human fibroblasts, then evaluated for their potential anticancer activities against colon (Caco-2) and breast (MDA-MB 231) cancers. The relatively lengthy bis-Mannich bases 15 and 16 were safer and more potent than 5-fluorouracil with sub-micromolar IC₅₀ and promising selectivity to the screened cancer cell lines rather than normal cells. Both compounds upregulated p53 (2–5.6-fold) and suppressed cyclin D expression (0.8–0.2-fold) in the studied cancers, and thus, induced apoptosis. 15 was superior to 16 in terms of cytotoxic activities, p53 induction, and cyclin D suppression. Mechanistically, both were efficient MMP-2/9 inhibitors with comparable potencies to the reference prototype hydroxamate-based MMP inhibitor NNGH at their anticancer IC₅₀ concentrations. 15 (IC₅₀ = 0.143 µM) was 4-fold more potent than NNGH against MMP-9 with promising selectivity (3.27-fold) over MMP-2, whereas 16 was comparable to NNGH. Concerning MMP-2, 16 (IC₅₀ = 0.376 µM) was 1.2-fold more active than 15. Docking simulations predicted their possible binding modes and highlighted the possible structural determinants of MMP-2/9 inhibitory activities. Computational prediction of their physicochemical properties, ADMET, and drug-likeness metrics revealed acceptable drug-like criteria.     

Synthesis of 9-Hydroxy-1H-Benzo[f]chromene Derivatives with Effective Cytotoxic Activity on MCF7/ADR,P-Glycoprotein Inhibitors,Cell Cycle Arrest and Apoptosis Effects

β-Enaminonitriles bearing 9-hydroxy-1H-benzo[f]chromene moiety was synthesized. The targeted compounds were evaluated for their anti-proliferative activity against three human tumor cell lines, PC-3, SKOV-3 and HeLa, and the active cytotoxic compounds were further evaluated against cancer cells, MCF-7/ADR, and two normal cell lines, HFL-1 and WI-38. Few compounds were assigned to be the most potent derivatives against PC-3, SKOV-3 and HeLa cell lines in comparison with Vinblastine and Doxorubicin. Several compounds possessed a relatively good potency against MCF-7/ADR cells as compared with Doxorubicin and were tested as a P-gp inhibitor. Moreover, the halogenated substituents, 2,4-F₂, 2,3-Cl₂, 2,5-Cl₂ and 3,4-Cl_2; have good potency against P-gp-mediated MDR in MCF-7/ADR as compared with Doxorubicin. Meanwhile, Rho123 accumulation assays revealed that few compounds effectively inhibited P-pg and efflux function. In addition, certain derivatives induced apoptosis and an accumulation of the treated MCF-7/ADR cells in the G1, S and G1/S phases.     

Vulnerability Assessment of Water Resources Systems in the Eastern Nile Basin

Planning effective joint development programs in shared river basins is thought to become better when such programs are preceded by integrated studies. This paper aims to provide such a study through a situation analysis with regard to the vulnerability of water resources systems in the Eastern Nile Basin (ENB). The focus was on using internationally recognized indicators and indices that can provide an insight about the situation in the region in a concise and illustrative fashion. A framework for assessing vulnerability of water systems was outlined and applied to the region. Based on a careful survey, a list of 31 indicators used for vulnerability assessment were identified and categorized to separate hydro-physical indicators from other indicators of socio-economic or political nature. The identified indicators were evaluated for the three ENB countries and illustrated in radar diagrams. Interpretations were drawn describing the vulnerability situation in each country. The main findings are: (1) vulnerability of water resources is highest in Sudan, followed by Ethiopia and then Egypt; (2) while vulnerability in Egypt stems mainly from hydro-physical factors; in Sudan and Ethiopia it is directly related to poverty and underdevelopment; (3) Higher stresses on available water resources in Egypt are due to increases in total withdrawals; while in Sudan and Ethiopia it is mainly due to water mal-distribution and quality deterioration; (4) governance factors in the three countries hinder the proper management of the available water resources.     

Luminescent Silicon Diatom Replicas: Self‐Reporting and Degradable Drug Carriers with Biologically Derived Shape for Sustained Delivery of Therapeutics

Current development of drug microcarriers is mainly based on spherical shapes, which are not biologically favorable geometries for complex interactions with biological systems. Scalable synthesis of drug carriers with nonspherical and anisotropic shapes featuring sustained drug‐releasing performances, biocompatibility, degradability, and sensing capabilities is challenging. These challenges are addressed in this work by employing Nature's optimized designs obtained from low‐cost diatomaceous earth mineral derived from single‐cell algae diatoms. Silica diatoms with unique shapes and 3D microcapsule morphology are converted into silicon diatom replicas with identical structure by a magnesiothermic reduction process. The results reveal that prepared silicon diatoms have a set of unique properties including favorable microcapsule structure with high surface area and micro/mesoporosity providing high drug loading, fast biodegradability, and intrinsic luminescence, which make them highly suitable for low‐cost production of advanced drug microcarriers. Their sustained drug release >30 days combined with self‐reporting function based on silicon luminescence properties using nonluminescent and luminescent drugs for intravitreal drug therapy is successfully demonstrated. These silicon diatoms offer promising potential toward scalable production of low‐cost and advanced microcarriers for broad medical therapies, including theranostics and microrobotic guided drug delivery devices.     

Isolation and structure determination of new nematicidal triglyceride fromArgemone mexicana

The petroleum ether extract ofArgemone mexicana seeds was found to possess nematicidal activity against the plant parasitic nematodeMeloidogyne incognita. The active nematicidal compound has been isolated from the crude extract by column Chromatographic techniques and purified by TLC. Chemical structure has been determined by chemical and spectro-scopic methods to be that of a triglyceride, sn-glycerol-1-eicosa-9, 12-dien-oate-2-palmitoleate-3-linoleate.     

Stability and magnetically induced heating behavior of lipid-coated Fe3O4 nanoparticles

Magnetic nanoparticles that are currently explored for various biomedical applications exhibit a high propensity to minimize total surface energy through aggregation. This study introduces a unique, thermoresponsive nanocomposite design demonstrating substantial colloidal stability of superparamagnetic Fe₃O₄ nanoparticles (SPIONs) due to a surface-immobilized lipid layer. Lipid coating was accomplished in different buffer systems, pH 7.4, using an equimolar mixture of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and l-α-dipalmitoylphosphatidyl glycerol (DPPG). Particle size and zeta potential were measured by dynamic laser light scattering. Heating behavior within an alternating magnetic field was compared between the commercial MFG-1000 magnetic field generator at 7 mT (1 MHz) and an experimental, laboratory-made magnetic hyperthermia system at 16.6 mT (13.7 MHz). The results revealed that product quality of lipid-coated SPIONs was significantly dependent on the colloidal stability of uncoated SPIONs during the coating process. Greatest stability was achieved at 0.02 mg/mL in citrate buffer (mean diameter = 80.0 ± 1.7 nm; zeta potential = -47.1 ± 2.6 mV). Surface immobilization of an equimolar DPPC/DPPG layer effectively reduced the impact of buffer components on particle aggregation. Most stable suspensions of lipid-coated nanoparticles were obtained at 0.02 mg/mL in citrate buffer (mean diameter = 179.3 ± 13.9 nm; zeta potential = -19.1 ± 2.3 mV). The configuration of the magnetic field generator significantly affected the heating properties of fabricated SPIONs. Heating rates of uncoated nanoparticles were substantially dependent on buffer composition but less influenced by particle concentration. In contrast, thermal behavior of lipid-coated nanoparticles within an alternating magnetic field was less influenced by suspension vehicle but dramatically more sensitive to particle concentration. These results underline the advantages of lipid-coated SPIONs on colloidal stability without compromising magnetically induced hyperthermia properties. Since phospholipids are biocompatible, these unique lipid-coated Fe₃O₄ nanoparticles offer exciting opportunities as thermoresponsive drug delivery carriers for targeted, stimulus-induced therapeutic interventions.

PACS

7550Mw; 7575Cd; 8185Qr     

Novel PEGylated Nanoassemblies Made of Self‐Assembled Squalenoyl Nucleoside Analogues

This study describes a new simple method to obtain high loading of anticancer or antiviral nucleoside analogues into “stealth” poly(ethylene glycol) (PEG)‐coated nanoassemblies. These nanodevices are obtained by co‐nanoprecipitation in water of (i) squalenoyl prodrugs obtained by the bioconjugation of the natural lipid squalene with either the anticancer drug gemcitabine (Gem‐Sq) or the antiviral drug deoxycytidine (ddC‐Sq) with (ii) a PEG derivative of either cholesterol (Chol‐PEG) or squalene (Sq‐PEG). It was found that both PEG derivatives (Chol‐PEG or Sq‐PEG) were efficiently incorporated in the resulting composite nanoassemblies (CNAs), as shown by radioactivity studies, Zeta potential determination, and size measurements. Optimal compositions were defined for each PEG derivative to ensure the best stability in water and in buffer solutions. X‐ray diffraction and electron microscopy investigations revealed that depending on the structure of the squalenoyl nucleoside analogue used (Gem‐Sq or ddC‐Sq), these nanoassemblies might be toroids or cubosomes. Following PEGylation, the Gem‐Sq nanoassemblies displayed superior in vitro anticancer activity on gemcitabine‐resistant leukemia L1210 10K cells than either their non‐PEGylated counterparts or gemcitabine alone.