Nanoformulation of dasatinib cannot overcome therapy resistance of pancreatic cancer cells with low LYN kinase expression.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most difficult to treat tumors. The Src (sarcoma) inhibitor dasatinib (DASA) has shown promising efficacy in preclinical studies of PDAC. However, clinical confirmation could not be achieved. Overall, our aim was to deliver arguments for the possible reinitiating clinical testing of this compound in a biomarker-stratifying therapy trial for PDAC patients. We tested if the nanofunctionalization of DASA can increase the drug efficacy and whether certain Src members can function as clinical predictive biomarkers. METHODS: Methods include manufacturing of poly(vinyl alcohol) stabilized gold nanoparticles and their drug loading, dynamic light scattering, transmission electron microscopy, thermogravimetric analysis, Zeta potential measurement, sterile human cell culture, cell growth quantification, accessing and evaluating transcriptome and clinical data from molecular tumor dataset TCGA, as well as various statistical analyses. RESULTS: We generated homo-dispersed nanofunctionalized DASA as an AuNP@PVA-DASA conjugate. The composite did not enhance the anti-growth effect of DASA on PDAC cell lines. The cell model with high LYN expression showed the strongest response to the therapy. We confirm deregulated Src kinetome activity as a prevalent feature of PDAC by revealing mRNA levels associated with higher malignancy grade of tumors. BLK (B lymphocyte kinase) expression predicts shorter overall survival of diabetic PDAC patients. CONCLUSIONS: Nanofunctionalization of DASA needs further improvement to overcome the therapy resistance of PDAC. LYN mRNA is augmented in tumors with higher malignancy and can serve as a predictive biomarker for the therapy resistance of PDAC cells against DASA. Studying the biological roles of BLK might help to identify underlying molecular mechanisms associated with PDAC in diabetic patients.

Novel Re(I) Complexes as Potential Selective Theranostic Agents in Cancer Cells and In Vivo in Caenorhabditis elegans Tumoral Strains.

A series of rhenium(I) complexes of the type fac-[Re(CO)3(N^N)L]0/+, Re1-Re9, was synthesized, where N^N = benzimidazole-derived bidentate ligand with an ester functionality and L = chloride or pyridine-type ligand. The new compounds demonstrated potent activity toward ovarian A2780 cancer cells. The most active complexes, Re7-Re9, incorporating 4-NMe2py, exhibited remarkable activity in 3D HeLa spheroids. The emission in the red region of Re9, which contains an electron-deficient benzothiazole moiety, allowed its operability as a bioimaging tool for in vitro and in vivo visualization. Re9 effectivity was tested in two different C. elegans tumoral strains, JK1466 and MT2124, to broaden the oncogenic pathways studied. The results showed that Re9 was able to reduce the tumor growth in both strains by increasing the ROS production inside the cells. Moreover, the selectivity of the compound toward cancerous cells was remarkable as it did not affect neither the development nor the progeny of the nematodes.

Indole Diketopiperazine Alkaloids from the Marine Sediment-Derived Fungus Aspergillus chevalieri against Pancreatic Ductal Adenocarcinoma.

A new prenylated indole diketopiperazine alkaloid, rubrumline P (1), was isolated along with six more analogues and characterized from the fermentation culture of a marine sediment-derived fungus, Aspergillus chevalieri, collected at a depth of 15 m near the lighthouse in Dahab, Red Sea, Egypt. In the current study, a bioassay-guided fractionation allowed for the identification of an active fraction displaying significant cytotoxic activity against the human pancreatic adenocarcinoma cell line PANC-1 from the EtOAc extract of the investigated fungus compared to the standard paclitaxel. The structures of the isolated compounds from the active fraction were established using 1D/2D NMR spectroscopy and mass spectrometry, together with comparisons with the literature. The absolute configuration of the obtained indole diketopiperazines was established based on single-crystal X-ray diffraction analyses of rubrumline I (2) and comparisons of optical rotations and NMR data, as well as on biogenetic considerations. Genome sequencing indicated the formation of prenyltransferases, which was subsequently confirmed by the isolation of mono-, di-, tri-, and tetraprenylated compounds. Compounds rubrumline P (1) and neoechinulin D (4) confirmed preferential cytotoxic activity against PANC-1 cancer cells with IC50 values of 25.8 and 23.4 µM, respectively. Although the underlying mechanism-of-action remains elusive in this study, cell cycle analysis indicated a slight increase in the sub-G1 peak after treatment with compounds 1 and 4.

The Complexity of Comparative Adsorption of C6 Hydrocarbons (Benzene, Cyclohexane, n-Hexane) at Metal-Organic Frameworks.

The relatively stable MOFs Alfum, MIL-160, DUT-4, DUT-5, MIL-53-TDC, MIL-53, UiO-66, UiO-66-NH2, UiO-66(F)4, UiO-67, DUT-67, NH2-MIL-125, MIL-125, MIL-101(Cr), ZIF-8, ZIF-11 and ZIF-7 were studied for their C6 sorption properties. An understanding of the uptake of the larger C6 molecules cannot simply be achieved with surface area and pore volume (from N2 sorption) but involves the complex micropore structure of the MOF. The maximum adsorption capacity at p p0-1 = 0.9 was shown by DUT-4 for benzene, MIL-101(Cr) for cyclohexane and DUT-5 for n-hexane. In the low-pressure range from p p0-1 = 0.1 down to 0.05 the highest benzene uptake is given by DUT-5, DUT-67/UiO-67 and MIL-101(Cr), for cyclohexane and n-hexane by DUT-5, UiO-67 and MIL-101(Cr). The highest uptake capacity at p p0-1 = 0.02 was seen with MIL-53 for benzene, MIL-125 for cyclohexane and DUT-5 for n-hexane. DUT-5 and MIL-101(Cr) are the MOFs with the widest pore window openings/cross sections but the low-pressure uptake seems to be controlled by a complex combination of ligand and pore-size effect. IAST selectivities between the three binary mixtures show a finely tuned and difficult to predict interplay of pore window size with (critical) adsorptive size and possibly a role of electrostatics through functional groups such as NH2.

CD133-Functionalized Gold Nanoparticles as a Carrier Platform for Telaglenastat (CB-839) against Tumor Stem Cells.

The failure of a long-lasting curative therapeutic benefit of currently applied chemotherapies against malignant cancers is suggested to be caused by the ineffectiveness of such interventions on cancer stem cells (CSCs). CD133/AC133 is a cell surface protein previously shown to have potential to identify CSCs in various tumors, including brain tumors. Moreover, an increase in the rate of cellular metabolism of glutamine and glucose are contributors to the fast cellular proliferation of some high-grade malignancies. Inhibition of glutaminolysis by utilizing pharmacological inhibitors of the enzyme glutaminase 1 (GLS1) can be an effective anti-CSC strategy. In this study, the clinical-stage GLS1 inhibitor Telaglenastat (CB-839) was loaded into PEGylated gold nanoparticles equipped with the covalently conjugated CD133 aptamer (Au-PEG-CD133-CB-839) and exposed to a collection of CD133-positive brain tumor models in vitro. Our results show that Au-PEG-CD133-CB-839 significantly decreased the viability of CD133-postive cancer cells in a dose-dependent manner, which was higher as compared to the effects of treatment of the cells with the individual components of the assembled nanodrug. Interestingly, the treatment effect was observed in glioblastoma stem cells modeling different transcriptomic subtypes of the disease. The presented platform is the fundament for subsequent target specificity characterization and in vivo application.

Nickel-Based Metal-Organic Frameworks as Electrocatalysts for the Oxygen Evolution Reaction (OER).

The exploration of earth-abundant electrocatalysts with high performance for the oxygen evolution reaction (OER) is eminently desirable and remains a significant challenge. The composite of the metal-organic framework (MOF) Ni10Co-BTC (BTC = 1,3,5-benzenetricarboxylate) and the highly conductive carbon material ketjenblack (KB) could be easily obtained from the MOF synthesis in the presence of KB in a one-step solvothermal reaction. The composite and the pristine MOF perform better than commercially available Ni/NiO nanoparticles under the same conditions for the OER. Activation of the nickel-cobalt clusters from the MOF can be seen under the applied anodic potential, which steadily boosts the OER performance. Ni10Co-BTC and Ni10Co-BTC/KB are used as sacrificial agents and undergo structural changes during electrochemical measurements, the stabilized materials show good OER performances.

A Preclinical Pipeline for Translational Precision Medicine-Experiences from a Transdisciplinary Brain Tumor Stem Cell Project.

Efficient transdisciplinary cooperation promotes the rapid discovery and clinical application of new technologies, especially in the competitive sector of oncology. In this review, written from a clinical-scientist point of view, we used glioblastoma-the most common and most aggressive primary brain tumor as a model disease with a largely unmet clinical need, despite decades of intensive research-to promote transdisciplinary medicine. Glioblastoma stem-like cells (GSCs), a special tumoral cell population analogue to healthy stem cells, are considered largely responsible for the progression of the disease and the mediation of therapy resistance. The presented work followed the concept of translational science, which generates the theoretical backbones of translational research projects, and aimed to close the preclinical gap between basic research and clinical application. Thus, this generated an integrated translational precision medicine pipeline model based on recent theoretical and experimental publications, which supports the accelerated discovery and development of new paths in the treatment of GSCs. The work may be of interest to the general field of precision medicine beyond the field of neuro-oncology such as in Cancer Neuroscience.

Covalent Triazine Frameworks Based on the First Pseudo-Octahedral Hexanitrile Monomer via Nitrile Trimerization: Synthesis, Porosity, and CO2 Gas Sorption Properties.

Herein, we report the first synthesis of covalent triazine-based frameworks (CTFs) based on a hexanitrile monomer, namely the novel pseudo-octahedral hexanitrile 1,4-bis(tris(4'-cyano-phenyl)methyl)benzene 1 using both ionothermal reaction conditions with ZnCl2 at 400 °C and the milder reaction conditions with the strong Brønsted acid trifluoromethanesulfonic acid (TFMS) at room temperature. Additionally, the hexanitrile was combined with different di-, tri-, and tetranitriles as a second linker based on recent work of mixed-linker CTFs, which showed enhanced carbon dioxide captures. The obtained framework structures were characterized via infrared (IR) spectroscopy, elemental analysis, scanning electron microscopy (SEM), and gas sorption measurements. Nitrogen adsorption measurements were performed at 77 K to determine the Brunauer-Emmett-Teller (BET) surface areas range from 493 m2/g to 1728 m2/g (p/p0 = 0.01-0.05). As expected, the framework CTF-hex6 synthesized from 1 with ZnCl2 possesses the highest surface area for nitrogen adsorption. On the other hand, the mixed framework structure CTF-hex4 formed from the hexanitrile 1 and 1,3,5 tricyanobenzene (4) shows the highest uptake of carbon dioxide and methane of 76.4 cm3/g and 26.6 cm3/g, respectively, at 273 K.

A 2-(benzothiazol-2-yl)-phenolato platinum(II) complex as potential photosensitizer for combating bacterial infections in lung cancer chemotherapy†.

Cancer and antibiotic resistance are two global health threats that usually hamper clinical chemotherapeutic efficacy. Particularly for lung cancer, bacterial infections frequently arise thereby complicating the course of cancer treatment. In this sense, three new neutral luminescent cycloplatinated(II) photosensitizers of the type [Pt(dmba)(L)] (dmba = N,N-dimethylbenzylamine-κN,κC; L = 2-(benzo[d]oxazol-2-yl)-phenolato-κN,κO1, 2-(benzo[d]thiazol-2-yl)-phenolato-κN,κO2, and 2-(1-methyl-1H-benzo[d]imidazole-2-yl)phenolato-κN,κO3) have been characterized and developed to potentially eliminate both resistant bacteria and lung cancer cells. The phototherapeutic effects of complex 2 have been evaluated using low doses of blue light irradiation. Complex 2 exerted promising photoactivity against pathogenic Gram-positive bacteria strains of clinical interest, displaying a phototoxic index (PI) of 15 for methicillin-resistant Staphylococcus aureus, one of the major microorganisms predominating lung infections. Likewise, the anticancer activity of 2 was also increased upon light irradiation in human lung A549 cancer cells (PI = 36). Further in vitro experiments with this platinum(II) complex suggest that ROS-generating photodynamic reactions were involved upon light irradiation, thus providing a reasonable mechanism for its dual anticancer and antibacterial activities.

Zirconium and Aluminum MOFs for Low-Pressure SO2 Adsorption and Potential Separation: Elucidating the Effect of Small Pores and NH2 Groups.

Finding new adsorbents for the desulfurization of flue gases is a challenging task but is of current interest, as even low SO2 emissions impair the environment and health. Four Zr- and eight Al-MOFs (Zr-Fum, DUT-67(Zr), NU-1000, MOF-808, Al-Fum, MIL-53(Al), NH2-MIL-53(Al), MIL-53(tdc)(Al), CAU-10-H, MIL-96(Al), MIL-100(Al), NH2-MIL-101(Al)) were examined toward their SO2 sorption capability. Pore sizes in the range of about 4-8 Å are optimal for SO2 uptake in the low-pressure range (up to 0.1 bar). Pore widths that are only slightly larger than the kinetic diameter of 4.1 Å of the SO2 molecules allow for multi-side-dispersive interactions, which translate into high affinity at low pressure. Frameworks NH2-MIL-53(Al) and NH2-MIL-101(Al) with an NH2-group at the linker tend to show enhanced SO2 affinity. Moreover, from single-gas adsorption isotherms, ideal adsorbed solution theory (IAST) selectivities toward binary SO2/CO2 gas mixtures were determined with selectivity values between 35 and 53 at a molar fraction of 0.01 SO2 (10.000 ppm) and 1 bar for the frameworks Zr-Fum, MOF-808, NH2-MIL-53(Al), and Al-Fum. Stability tests with exposure to dry SO2 during ≤10 h and humid SO2 during 5 h showed full retention of crystallinity and porosity for Zr-Fum and DUT-67(Zr). However, NU-1000, MOF-808, Al-Fum, MIL-53(tdc), CAU-10-H, and MIL-100(Al) exhibited ≥50-90% retained Brunauer-Emmett-Teller (BET)-surface area and pore volume; while NH2-MIL-100(Al) and MIL-96(Al) demonstrated a major loss of porosity under dry SO2 and MIL-53(Al) and NH2-MIL-53(Al) under humid SO2. SO2 binding sites were revealed by density functional theory (DFT) simulation calculations with adsorption energies of -40 to -50 kJ·mol-1 for Zr-Fum and Al-Fum and even above -50 kJ·mol-1 for NH2-MIL-53(Al), in agreement with the isosteric heat of adsorption near zero coverage (ΔHads0). The predominant, highest binding energy noncovalent binding modes in both Zr-Fum and Al-Fum feature µ-OHδ+···Î´-OSO hydrogen bonding interactions. The small pores of Al-Fum allow the interaction of two µ-OH bridges from opposite pore walls with the same SO2 molecule via OHδ+···Î´-OSOδ-···Î´+HO hydrogen bonds. For NH2-MIL-53(Al), the DFT high-energy binding sites involve NHδ+···Î´-OS together with the also present Al-µ-OHδ+···Î´-OS hydrogen bonding interactions and C6-πδ-···Î´+SO2, Nδ-···Î´+SO2 interactions.

Nickel nanoparticle-decorated reduced graphene oxide/WO3 nanocomposite - a promising candidate for gas sensing.

We report for the first time the combination of WO3 sensing elements with a non-noble metal-carbon composite, namely a nickel metal nanoparticle-carbon composite (Ni@rGO). Previous work with WO3 had used either NiO (as part of the WO3 lattice), solely carbon, Pd-surface decorated WO3 (Pd@WO3), or Pd or Pt@carbon@WO3. We demonstrate the gas response for pure WO3, rGO/WO3 and Ni@rGO/WO3 sensing elements towards NO2 and acetone in air as well as towards CO in N2. The addition of 0.35 wt % Ni@rGO composite to WO3 enables the increase of the sensory response by more than 1.6 times for NO2 vapors. The gas response towards acetone using 0.35 wt % Ni@rGO/WO3 composite was 1.5 times greater for 3500 ppm than for 35,000 ppm acetone. For 0.35 wt % Ni@rGO/WO3 composite and CO gas, a response time (T res) of 7 min and a recovery time (T rec) of 2 min was determined.

Augmented Therapeutic Potential of Glutaminase Inhibitor CB839 in Glioblastoma Stem Cells Using Gold Nanoparticle Delivery.

Gold nanoparticles (Au NPs) are studied as delivery systems to enhance the effect of the glutaminase1 inhibitor CB839, a promising drug candidate already in clinical trials for tumor treatments. Au NPs were synthesized using a bottom-up approach and covered with polymers able to bind CB839 as a Au-polymer-CB839 conjugate. The drug loading efficiency (DLE) was determined using high-performance liquid chromatography and characterization of the CB839-loaded NPs was done with various microscopic and spectroscopic methods. Despite the chemical inertness of CB839, Au NPs were efficient carriers with a DLE of up to 12%, depending on the polymer used. The therapeutic effect of CB839 with and without Au was assessed in vitro in 2D and 3D glioblastoma (GBM) cell models using different assays based on the colony formation ability of GBM stem cells (GSCs). To avoid readout disturbances from the Au metal, viability methods which do not require optical detection were hereby optimized. These showed that Au NP delivery increased the efficacy of CB839 in GSCs, compared to CB839 alone. Fluorescent microscopy proved successful NP penetration into the GSCs. With this first attempt to combine CB839 with Au nanotechnology, we hope to overcome delivery hurdles of this pharmacotherapy and increase bioavailability in target sites.

Organoplatinum(II) Complexes Self-Assemble and Recognize AT-Rich Duplex DNA Sequences.

The specific recognition of AT-rich DNA sequences opens up the door to promising diagnostic and/or therapeutic strategies against gene-related diseases. Here, we demonstrate that amphiphilic PtII complexes of the type [Pt(dmba)(N∧N)]NO3 (dmba = N,N-dimethylbenzylamine-κN, κC; N∧N = dpq (3), dppz (4), and dppn (5)) recognize AT-rich oligonucleotides over other types of DNA, RNA, and model proteins. The crystal structure of 4 shows the presence of significant π-stacking interactions and a distorted coordination sphere of the d8 PtII atom. Complex 5, containing the largest π-conjugated ligand, forms supramolecular assemblies at high concentrations under aqueous environment. However, its aggregation can be promoted in the presence of DNA at concentrations as low as 10 µM in a process that "turns on" its excimer emission around 600 nm. Viscometry, gel electrophoresis, and theoretical calculations demonstrate that 5 binds to minor groove when self-assembled, while the monomers of 3 and 4 intercalate into the DNA. The complexes also inhibit cancer cell growth with low-micromolar IC50 values in 2D tissue culture and suppress tumor growth in 3D tumor spheroids with a multicellular resistance (MCR) index comparable to that of cisplatin.

Isocyanide-based consecutive Bargellini/Ugi reactions: an efficient method for the synthesis of pseudo-peptides containing three amide bonds.

Isocyanide-based consecutive Bargellini/Ugi multicomponent reactions as a combinatorial strategy have been developed for the synthesis of new class of pseudo-peptides. Via Bargellini reaction 3-carboxamido-isobutyric acids are prepared using acetone, chloroform, sodium hydroxide, and isocyanides. Then, using Ugi multicomponent reaction strategy, pseudo-peptides containing three amide bonds are synthesized using the Bargellini reaction product, aldehydes, amines, and isocyanides. This is an efficient and eco-friendly approach for easy access to wide variety of structurally diverse, drug-like pseudo-peptides from cheap and readily available precursors in high yields.

Enzymatic Activity of CD73 Modulates Invasion of Gliomas via Epithelial-Mesenchymal Transition-Like Reprogramming.

Glioblastoma (GBM) is the most aggressive malignant primary brain tumour in adulthood. Despite strong research efforts current treatment options have a limited impact on glioma stem-like cells (GSCs) which contribute to GBM formation, progression and chemoresistance. Invasive growth of GSCs is in part associated with epithelial-mesenchymal-like transition (EMT), a mechanism associated with CD73 in several cancers. Here, we show that CD73 regulates the EMT activator SNAIL1 and further investigate the role of enzymatic and non-enzymatic CD73 activity in GBM progression. Reduction of CD73 protein resulted in significant suppression of GSC viability, proliferation and clonogenicity, whereas CD73 enzymatic activity exhibited negative effects only on GSC invasion involving impaired downstream adenosine (ADO) signalling. Furthermore, application of phosphodiesterase inhibitor pentoxifylline, a potent immunomodulator, effectively inhibited ZEB1 and CD73 expression and significantly decreased viability, clonogenicity, and invasion of GSC in vitro cultures. Given the involvement of adenosine and A3 adenosine receptor in GSC invasion, we investigated the effect of the pharmacological inhibition of A3AR on GSC maintenance. Direct A3AR inhibition promoted apoptotic cell death and impaired the clonogenicity of GSC cultures. Taken together, our data indicate that CD73 is an exciting novel target in GBM therapy. Moreover, pharmacological interference, resulting in disturbed ADO signalling, provides new opportunities to innovate GBM therapy.

Nickel nanoparticles supported on a covalent triazine framework as electrocatalyst for oxygen evolution reaction and oxygen reduction reactions.

Covalent triazine frameworks (CTFs) are little investigated, albeit they are promising candidates for electrocatalysis, especially for the oxygen evolution reaction (OER). In this work, nickel nanoparticles (from Ni(COD)2) were supported on CTF-1 materials, which were synthesized from 1,4-dicyanobenzene at 400 °C and 600 °C by the ionothermal method. CTF-1-600 and Ni/CTF-1-600 show high catalytic activity towards OER and a clear activity for the electrochemical oxygen reduction reaction (ORR). Ni/CTF-1-600 requires 374 mV overpotential in OER to reach 10 mA/cm2, which outperforms the benchmark RuO2 catalyst, which requires 403 mV under the same conditions. Ni/CTF-1-600 displays an OER catalytic activity comparable with many nickel-based electrocatalysts and is a potential candidate for OER. The same Ni/CTF-1-600 material shows a half-wave potential of 0.775 V for ORR, which is slightly lower than that of commercial Pt/C (0.890 V). Additionally, after accelerated durability tests of 2000 cycles, the material showed only a slight decrease in activity towards both OER and ORR, demonstrating its superior stability.

Probing the limits of linker substitution in aluminum MOFs through water vapor sorption studies: mixed-MOFs instead of mixed-linker CAU-23 and MIL-160 materials.

We report a systematic study on the possibility of forming mixed-linker metal-organic frameworks (MOFs) spanning between the aluminum MOFs CAU-23 and MIL-160 with their 2,5-thiophenedicarboxylate (TDC) and 2,5-furandicarboxylate (FDC) linkers, respectively. The planned synthesis of a mixed-linker MOF, combining TDC and FDC in the framework turned out to yield a rather largely intricate mixture of CAU-23 and MIL-160. This is due to the different opening angles of 150° for TDC versus 120° for FDC and the concomitant cis-trans versus cis-only OH-bridges in the infinite secondary building unit {Al(µ-OH)(O2C-)} chains. At the same time, the CAU-23 phase is accompanied by the polymorphic MIL-53-TDC phase with trans-only OH-bridges. The measurement of water vapor sorption isotherms was the method of choice to confirm the formation of mixed MOFs instead of mixed-linker phases. Thereby, the water sorption isotherms indicate the simultaneous formation of both MOF phases, albeit they do not exclude mixed-linker MOFs which may have formed at low levels of substitution. The differentiation via powder X-ray diffractometry (PXRD), IR-spectroscopy and nitrogen sorption was either not conclusive enough or impossible, due to similarities of the neat MOF phases. The synthesized MOF mixtures within the TDC : FDC ratios of 38 : 62 up to 82 : 18 exhibit two or three uptake steps in the water sorption isotherm, with the first two corresponding to an overlay from the individual water sorption isotherm of CAU-23 and MIL-160 and a third one from the additional MIL-53-TDC.

Azaphilones from the Red Sea Fungus Aspergillus falconensis.

The marine-derived fungus Aspergillus falconensis, isolated from sediment collected from the Canyon at Dahab, Red Sea, yielded two new chlorinated azaphilones, falconensins O and P (1 and 2) in addition to four known azaphilone derivatives (3-6) following fermentation of the fungus on solid rice medium containing 3.5% NaCl. Replacing NaCl with 3.5% NaBr induced accumulation of three additional new azaphilones, falconensins Q-S (7-9) including two brominated derivatives (7 and 8) together with three known analogues (10-12). The structures of the new compounds were elucidated by 1D and 2D NMR spectroscopy and HRESIMS data as well as by comparison with the literature. The absolute configuration of the azaphilone derivatives was established based on single-crystal X-ray diffraction analysis of 5, comparison of NMR data and optical rotations as well as on biogenetic considerations. Compounds 1, 3-9, and 11 showed NF-κB inhibitory activity against the triple negative breast cancer cell line MDA-MB-231 with IC50 values ranging from 11.9 to 72.0 µM.

High performance MIL-101(Cr)@6FDA-mPD and MOF-199@6FDA-mPD mixed-matrix membranes for CO2/CH4 separation.

Combination of the polyimide 6FDA-mPD (6FDA = 4,4'-hexafluoroisopropylidene diphthalic anhydride and mPD = m-phenylenediamine) and crystallites of the metal-organic frameworks (MOFs) MIL-101(Cr) or MOF-199 (HKUST-1, Cu-BTC) produces mixed-matrix membranes (MMMs) with excellent dispersion and compatibility of the MOF particles within the polymer matrix. Permeation tests of a binary CO2/CH4 (50/50) gas mixture showed a remarkable increase of CO2 permeabilities for MIL-101(Cr)@6FDA-mPD and significantly higher selectivities for MOF-199@6FDA-mPD. The CO2 permeability increased from 10 (neat polymer) to 50 Barrer for the 24 wt% MIL-101(Cr)@6FDA-mPD membrane (with essentially constant selectivity) due to the high pore volume of MIL-101(Cr). The CO2/CH4 selectivity increased from 54 to 89 from the neat 6FDA-mPD polymer to the 24 wt% MOF-199@6FDA-mPD membrane, apparently due to the high CO2 adsorption capacity of MOF-199.

Anti-inflammatory, antiallergic and COVID-19 protease inhibitory activities of phytochemicals from the Jordanian hawksbeard: identification, structure-activity relationships, molecular modeling and impact on its folk medicinal uses.

On Wednesday 11th March, 2020, the world health organization (WHO) announced novel coronavirus (COVID-19, also called SARS-CoV-2) as a pandemic. Due to time shortage and lack of either a vaccine and/or an effective treatment, many trials focused on testing natural products to find out potential lead candidates. In this field, an edible and folk medicinal Jordanian plant Crepis sancta (Asteraceae) was selected for this study. Phytochemical investigation of its enriched polyphenolic extract afforded four eudesmane sesquiterpenes (1-4) together with (6S,9R)-roseoside (5) and five different methylated flavonols (6-10). Structure elucidation of isolated compounds was unambiguously determined based on HRESIMS, X-ray crystallography, and exhaustive 1D and 2D NMR experiments. All isolated compounds were assessed for their in vitro anti-inflammatory, antiallergic and in silico COVID-19 main protease (Mpro) inhibitory activities. Among the tested compounds, compounds 5-10 revealed potent anti-inflammatory, antiallergic and COVID-19 protease inhibitory activities. Chrysosplenetin (10) is considered as a promising anti-inflammatory and antiallergic lead structure adding to the phytotherapeutic pipeline. Moreover, its inhibitory activity against SARS-CoV-2 Mpro, supported by docking and molecular dynamic studies, strengthens its potential as a lead structure paving the way toward finding out a natural remedy to treat and/or to control the current COVID-19 pandemic.