Synthesis and biological evaluation of novel artemisone–piperazine–tetronamide hybrids

For the first time, six novel artemisone–piperazine–tetronamide hybrids (12a–f) were efficiently synthesised from dihydroartemisinin (DHA) and investigated for their in vitro cytotoxicity against some human cancer cells and benign cells. All the targets showed good cytotoxic activity in vitro. Hybrid 12a exhibited much better inhibitory activity against human liver cancer cell line SMMC-7721 (IC₅₀ = 0.03 ± 0.04 μM for 24 h) than the parent DHA (IC₅₀ > 0.7 μM), and two references, vincristine (VCR; IC₅₀ = 0.27 ± 0.03 μM) & cytosine arabinoside (ARA; IC₅₀ = 0.63 ± 0.04 μM). Furthermore, hybrid 12a had low toxicity against human benign liver cell line LO2 (IC₅₀ = 0.70 ± 0.02 μM for 24 h) compared with VCR, ARA, and DHA in vitro. Moreover, the inhibitory activity of hybrid 12a was obviously enhanced when human liver cancer cell line MHCC97H absorbed Fe²⁺in vitro.

Six novel artemisone–piperazine–tetronamide hybrids were efficiently synthesised and investigated for their cytotoxicity against some human cancer cells.     

A simple sensitive UFLC-MS/MS method for the simultaneous quantification of artesunate,dihydroartemisinin and quercetin in rat plasma and its application to pharmacokinetic studies

An ultrafast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) method was developed for the simultaneous estimation of artesunate (ART), dihydroartemisinin (DHA, an active metabolite of ART) and quercetin (QRT) in rat plasma. The separation was achieved using a Zorbax C₁₈ column (3 μm, 50 mm × 4.6 mm) as a stationary phase with a mobile phase of 0.1% formic acid (10% by volume) and methanol (90% by volume) at a flow rate of 0.4 mL min⁻¹ and an injection volume of 10 μL. Artemisinin (ATM) was used as the internal standard (IS). Mass detection was performed by electrospray ionization (ESI)-tandem mass spectrometry via multiple reaction monitoring (MRM) in positive mode except for QRT, where negative ionization was used. The extraction recoveries of ART, DHA, and QRT from plasma were found to be 91.05–99.62%, 95.12–98.56% and 89.35–98.90%, respectively. The developed method was validated and successfully applied to the quantitative analysis of ART, DHA and QRT in plasma samples after the oral administration of ART and ART–QRT pure drugs to rats at the dose of 5 mg kg⁻¹ each. The results reveal that the developed method can be further used for the quantification of the proposed combination drugs in nanoformulations.

An ultrafast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) method was developed for the simultaneous estimation of artesunate (ART), dihydroartemisinin (DHA, an active metabolite of ART) and quercetin (QRT) in rat plasma.     

Extraction of oil from wet Antarctic krill (Euphausia superba) using a subcritical dimethyl ether method

In this study, a novel method for obtaining high-quality krill oil from wet Antarctic krill by using subcritical dimethyl ether (SDE) was proposed. A response surface design was used to obtain the best SDE extraction parameters. The optimum extraction efficiency of 93.77 ± 0.92% was obtained at a stirring speed of 1030 rpm, temperature of 47 °C and dynamic extraction time of 90 min. Compared with n-hexane, ethanol, supercritical CO₂ and subcritical n-butane extraction, the krill oil extracted by SDE exhibited low peroxide values (1.46 ± 0.26 mmol kg⁻¹), high astaxanthin (218.06 ± 4.74 mg kg⁻¹), phosphatidylcholine (PC) (33.95 ± 0.65%), and phosphatidylethanolamine (PE) (11.67 ± 0.23%) content. Moreover, krill oil extracted by SDE has high levels of EPA (16.38 ± 0.05%) and DHA (7.91 ± 0.07%). SDE extraction proved to be an efficient and safe method for extraction of quality krill oil from wet Antarctic krill, and it could be a promising method for oil extraction in wet food in future.

In this study, a novel method for obtaining high-quality krill oil from wet Antarctic krill by using subcritical dimethyl ether (SDE) was proposed.     

Self-assembled membrane manufactured by metal–organic framework (UiO-66) coated γ-Al2O3 for cleaning oily seawater

In order to effectively clean oily seawater with anionic polyacrylamide (APAM), UiO-66 coated γ-Al₂O₃ (UA) composites were firstly synthesized using γ-Al₂O₃ as a template to induce the growth of high hydrophilic UiO-66 on its surface to form a uniform UA self-assembled membrane. The UA composites and self-assembled membrane were characterized and analyzed. Also, the membrane performance was investigated. The results show that the hydrophilicity of particles is enhanced with the water contact angle decreasing from 39.8° (γ-Al₂O₃ particles) to 26.2° (UA composites) by introducing the UiO-66 coating. Moreover, the UA self-assembled membrane performs attractive water yield and separation performance. The oil concentration in the permeate treated by the first class of UA self-assembled membrane declines apparently from 91.22 to 18.90 mg L⁻¹, while the water yield is as high as 657.89 L m⁻² h⁻¹. The reclaimed separation experiments show that the membrane materials could be recycled by calcination at 200 °C and hydraulic cleaning, which gives the material potential application in cleaning oily seawater.

The self-assembled membrane manufactured by UA composites exhibits excellent separation performance and water yield in the treatment of oily seawater.     

Co-delivery of dihydroartemisinin and docetaxel in pH-sensitive nanoparticles for treating metastatic breast cancer via the NF-κB/MMP-2 signal pathway

Metastasis is a major barrier in cancer chemotherapy. Prolonged circulation and rapid, specific intracellular drug release are two main goals in the development of nanoscale drug delivery systems to treat metastatic breast cancer. In this study, we investigated the anti-metastasis effect of docetaxel (DTX) in combination with dihydroartemisinin (DHA) in metastatic breast cancer 4T1 cells. We synthesized a pH-sensitive material 4-arm-PEG-DTX with a hydrazone bond and used it to construct nanoparticles that co-deliver DTX and DHA (D/D NPs). The D/D NPs had a mean size of 142.5 nm and approximately neutral zeta potential. The pH-sensitive nanoparticles allowed acid-triggered drug release at the tumor site, showing excellent cytotoxicity (IC50 = 7.0 μg mL⁻¹), cell cycle arrest and suppression of cell migration and invasion. The mechanisms underlying the anti-metastasis effect of the D/D NPs involved downregulation of the expression of p-AKT, NF-κB and MMP-2. Therefore, D/D NPs represent a new nanoscale drug delivery system for treating metastatic breast cancer, responding to the acidic tumor microenvironment to release the chemotherapeutic drugs.

Co-delivery DTX and DHA as acid-sensitive nanoparticles to exert synergistic effects for metastatic breast cancer therapy.     

High-aspect-ratio mushroom-like silica nanopillars immersed in air: epsilon-near-zero metamaterials mediated by a phonon-polaritonic anisotropy

Epsilon-near-zero metamaterials offer opportunities for intriguing electromagnetic-wave phenomena. Here we experimentally demonstrate that silica perpendicular nanopillars immersed in air exhibit a uniaxial epsilon-near-zero response mediated by phonon polaritons in the mid-infrared range. Unique mushroom-shaped heads on nanopillars play a crucial role to realize SiO₂ metamaterials over a large area in our self-assembled fabrication process with block copolymers, polystyrene-block-poly(dimethylsiloxane) (PS-b-PDMS). SiO₂ nanopillars having heights of 80 nm, 200 nm, and 300 nm (aspect ratios up to ∼13) are obtained after calcination at 450 °C and the electromagnetic responses are evaluated using a mid-infrared ellipsometric apparatus. For nanopillars with 200 nm height, the permittivity of the perpendicular component ε_⊥ approaches to near zero (0.2) while the parallel component ε_‖ shows a value of 1.8. The measured uniaxial epsilon-near-zero responses are excellently reproduced by the effective medium theory. Our results, therefore, indicate that SiO₂ nanopillars/air uniaxial epsilon-near-zero metamaterials in the mid-infrared range can be amenable to large scale fabrication.

High-aspect-ratio mushroom-like silica nanopillars fabricated from self-assembly of block-copolymers exhibit a uniaxial epsilon-near-zero response in the mid-infrared range.     

Pharmacokinetics and Ex Vivo Pharmacodynamic Antimalarial Activity of Dihydroartemisinin-Piperaquine in Patients with Uncomplicated Falciparum Malaria in Vietnam

Compared to healthy subjects, malaria patients show a reduction in the mean oral clearance (1.19 versus 5.87 liters/h/kg of body weight) and apparent volume of distribution (1.47 versus 8.02 liters/kg) of dihydroartemisinin in Vietnamese patients following treatment with dihydroartemisinin-piperaquine (Artekin) for uncomplicated Plasmodium falciparum. Dihydroartemisinin is responsible for most of the ex vivo antimalarial activity of dihydroartemisinin-piperaquine.Dihydroartemisinin-piperaquine (Artekin) is an artemisinin-based combination treatment (ACT) drug that is well tolerated and highly effective in the treatment of Plasmodium falciparum malaria in Southeast Asia and Africa, with cure rates typically greater than 95% following a standard 3-day course (8, 9, 15, 17). Despite its extensive use over the past 5 years, no data are available on the clinical pharmacokinetics of dihydroartemisinin in malaria patients following treatment with the ACT. Few studies have investigated the pharmacokinetics of piperaquine in malaria patients. The highly lipophilic drug exhibits biphasic disposition kinetics, with a large apparent volume of distribution, low oral clearance, and a lengthy elimination half-life of about 3 to 4 weeks in malaria patients treated with dihydroartemisinin-piperaquine (6, 18).The present study investigated the clinical pharmacokinetic properties of dihydroartemisinin and piperaquine after a 3-day course of dihydroartemisinin-piperaquine in the treatment of uncomplicated P. falciparum malaria in Vietnamese patients. In addition to assessing the in vivo response of the ACT, the ex vivo pharmacodynamic antimalarial activity of dihydroartemisinin-piperaquine in the patients'' plasma samples was investigated against two lines of P. falciparum. The study was conducted at Military Hospital 175 in Ho Chi Minh City, Vietnam, in 12 adult Vietnamese patients. The volunteers had to satisfy the following inclusion criteria: male, aged 17 to 55 years old, parasite density between 500 and 100,000 per μl of blood, axillary temperature of ≥37.5°C or a history of fever in the previous 24 h, written informed consent, and willing to be monitored for 35 days. The exclusion criteria were as follows: antimalarial treatment within the preceding 2 weeks, mixed plasmodial infection, and history of another serious medical disease. The patients acquired their infections in Binh Phuoc Province, about 120 km from Ho Chi Minh City. The patients stayed at the hospital for the entire 35-day follow-up period and because Ho Chi Minh City is free of malaria, the possibility of reinfection was avoided. Ethical approval for the study was obtained from the Review and Scientific Board of Military Hospital 175 and the Australian Defense Human Research Ethics Committee (ADHREC protocol 379/05).The patients were administered a weight-based 3-day course of dihydroartemisinin-piperaquine (Holleykin Pharmaceuticals, China) (each tablet contained 40 mg of dihydroartemisinin and 320 mg of piperaquine phosphate) at 2.4 mg of dihydroartemisinin per kg of body weight and 19.2 mg of piperaquine per kg of body weight per day, rounded up or down to the nearest half tablet, with day 0 being designated the first dose. Dihydroartemisinin-piperaquine was administered within 15 min of having a standard Vietnamese breakfast of rice, noodles, and meat to enhance the absorption of piperaquine (13). Parasitemia and axillary temperature were measured before commencement of treatment and then every 8 h afterwards to determine parasite and fever clearance times. Blood samples (7 ml) were collected at 0, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 10, and 12 h using an indwelling cannula kept patent with heparinized saline after the last dose of dihydroartemisinin-piperaquine on day 2. Subsequent heparinized blood samples were collected by venipuncture at days 3, 4, 7, 14, 21, 28, and 35 after commencement of treatment. Blood samples were centrifuged, and the separated plasma samples were stored at −25°C until transported on dry ice to Australia for drug analysis, which was within 12 months of collection.Plasma dihydroartemisinin concentrations were measured by liquid chromatography-tandem mass spectrometry, with a lower limit of quantification of 1 ng/ml (2). The values for overall precision of analysis for dihydroartemisinin, as defined by the percent coefficient of variation of spiked samples were 6.3% at 1 ng/ml, 5.7% at 20 ng/ml, 4.6% at 200 ng/ml, and 6.6% at 750 ng/ml. The corresponding inaccuracy values were 1.3%, 1.5%, 0.7%, and 3.2% for 1, 20, 200, and 750 ng/ml, respectively. Plasma piperaquine concentrations were measured by a validated high-performance liquid chromatography method, with a lower limit of quantification of 5 ng/ml (11). The precision values of the assay were 10.3% at 10 ng/ml, 6.8% at 100 ng/ml, 6.7% at 500 ng/ml, and 6.5% at 1,000 ng/ml. The corresponding inaccuracy values were 11.1%, 2.8%, 0.8%, and 0.5% for 10, 100, 500, and 1,000 ng/ml, respectively. Pharmacokinetic parameters (peak concentration [C_max], time to reach maximum concentration [T_max], area under the concentration-time curve from day 2 to the last data point [AUC_d2-ld] and from day 2 to infinity [AUC_d2-∞], terminal half-life [t_1/2], apparent oral clearance, and apparent volume of distribution) were determined from the plasma concentration-time data using noncompartmental methods.The ex vivo pharmacodynamic antimalarial activity of dihydroartemisinin-piperaquine was assessed by culturing malaria parasites in vitro in the presence of patients'' plasma samples collected after the last administration of dihydroartemisinin-piperaquine by the method of Kotecka et al. (10), with minor modifications. Briefly, patients'' plasma samples (50 μl) were serially diluted twofold on microtiter plates with drug-free human plasma. The in vitro drug susceptibility of two lines of P. falciparum (chloroquine-sensitive D6 and chloroquine-resistant K1) to dihydroartemisinin and piperaquine were determined in parallel with the patients'' plasma samples. Fifty microliters of spiked drug solutions prepared in human plasma were serially diluted twofold on microtiter plates using drug-free plasma. Inoculum (50 μl) was added to each well containing either the patient''s plasma samples or spiked drug solutions, so that the total cell suspension (100 μl) contained 50% plasma in hypoxanthine-free plain LPLF-RPMI 1640, with a final hematocrit of 2% and a parasitemia (>95% rings) of 1%. Tritiated hypoxanthine incorporation was used to determine the extents to which parasite growth was inhibited by different drug concentrations or dilutions of the patients'' plasma during 48 h of incubation. The inhibitory concentration (90% infective concentration [IC₉₀] for spiked drug samples) and inhibitory dilution (90% infective dose [ID₉₀] for patient plasma samples) were defined as the drug concentrations and the number of dilutions of the patient plasma sample, respectively, that produced a 90% inhibition of uptake of tritiated hypoxanthine by intraerythrocytic malaria parasites compared to drug-free plasma samples (controls).The mean (standard deviation) age of the patients was 26.3 (10.4) years, with a mean (standard deviation) weight of 56.5 (7.8) kg. The patients had an admission geometric mean parasitemia of 15,198 parasites/μl of blood (range, 738 to 79,310 parasites/μl) and a mean temperature (standard deviation) of 37.7°C (1.3°C), with 42% (5 of 12) of patients with fever. Treatment with dihydroartemisinin-piperaquine promptly reduced fever, with a median fever clearance time of 24 h (range, 16 to 48 h) and led to a rapid reduction in parasite density, with a median parasite clearance time of 28 h (range, 16 to 56 h). Over the 35-day follow-up period, there was no recurrence of infection in the patients. The mean content values of five dihydroartemisinin-piperaquine tablets were 105.4% ± 4.8% for dihydroartemisinin and 109.0% ± 1.1% for piperaquine. Although none of the patients reported treatment with antimalarial drugs 2 weeks before commencing dihydroartemisinin-piperaquine, no dihydroartemisinin or piperaquine was detected in their predose samples, which confirmed no recent treatment with either artesunate or CV8 (dihydroartemisinin-piperaquine-primaquine-trimethoprim).The mean plasma concentration-time profiles of dihydroartemisinin and piperaquine after a 3-day course of dihydroartemisinin-piperaquine are shown in Fig. ​Fig.1,1, and the pharmacokinetics of the two drugs are summarized in Table ​Table1.1. Because dihydroartemisinin is rapidly eliminated with a t_1/2 of about 1 h in healthy Vietnamese subjects (2) and does not accumulate with daily administration, we were able to compare the pharmacokinetics of dihydroartemisinin in the Vietnamese patients after the last daily dose of the 3-day course of dihydroartemisinin-piperaquine with values obtained in healthy Vietnamese subjects given a single dose of dihydroartemisinin-piperaquine (2). The mean C_max and AUC of dihydroartemisinin were markedly higher in the Vietnamese malaria patients than in the healthy Vietnamese subjects (C_max, 698 versus 176 ng/ml; AUC_d2-∞, 1,949 versus 398 ng·h/ml). Although the difference was not as large, Binh et al. (1) reported an approximately twofold-higher mean C_max (1,045 versus 480 ng/ml) and AUC (2,401 versus 932 ng·h/ml) of dihydroartemisinin in Vietnamese malaria patients compared with healthy subjects administered a single dose of dihydroartemisinin (120 mg) alone. Dihydroartemisinin was rapidly eliminated in the malaria patients with a t_1/2 of 0.85 ± 0.15 h. The apparent oral clearance and apparent volume of distribution of dihydroartemisinin were 4.9-fold lower (1.19 versus 5.87 liters/h/kg) and 5.5-fold lower (1.47 versus 8.02 liters/kg) in the Vietnamese malaria patients than in the healthy subjects, respectively (2). A reduction in clearance and contraction in the apparent volume of distribution has also been reported for other antimalarial drugs, such as mefloquine (7) and quinine (21), during the acute phase of malaria. A likely explanation for the increase in bioavailability of dihydroartemisinin in malaria patients compared with healthy subjects is a decrease in hepatic clearance of dihydroartemisinin due to malaria (1). Alpha-acid glycoprotein levels also increase during acute malaria (16), and similar to quinine, this may cause an increase in binding of the protein-bound dihydroartemisinin, with a reduction in the apparent volume of distribution of the drug (12).Open in a separate windowFIG. 1.Plasma dihydroartemisinin (○) and piperaquine (•) concentration-time profiles after the last dose of a 3-day course of dihydroartemisinin-piperaquine (2.4 mg of dihydroartemisinin per kg and 19.2 mg of piperaquine per kg daily) for the treatment of uncomplicated Plasmodium falciparum malaria in 12 Vietnamese patients. The values shown are means plus standard deviations (error bars). The inset shows the piperaquine concentrations from day 2 to day 35 after commencement of treatment. The ex vivo pharmacodynamic antimalarial activity profile (mean ID₉₀ values ▴) of patients'' plasma samples after dihydroartemisinin-piperaquine treatment is derived from the K1 line of P. falciparum.

TABLE 1.

Pharmacokinetic parameters of dihydroartemisinin and piperaquine in 12 Vietnamese patients with uncomplicated P. falciparum malaria^a

Enhancing the antitumor activity of tea polyphenols encapsulated in biodegradable nanogels by macromolecular self-assembly

Nanogels (NGs) with desirable stability have emerged as a promising platform for biomedical applications. Herein, a convenient approach was developed to encapsulate and protect tea polyphenols (TPs) by macromolecular self-assembly of lysozyme (Ly) and carboxymethyl cellulose (CMC) through a heating treatment. Biodegradable Ly–CMC NGs were formed on the basis of molecules driven by electrostatic interaction and hydrophobic forces. The particle size and morphology of the Ly–CMC NGs were analyzed using a Malvern particle size analyzer, fluorescence spectrophotometer, and scanning electron microscope. The results showed that the heated NGs were spherical with better stability and smaller particle size. The encapsulation efficiency of TP-loaded NGs was 89.05 ± 3.14%, and it indicated that the Ly–CMC NGs may have a strong binding force with TPs. Moreover, TP-loaded NGs showed a sustained release feature. The DPPH and ABTS-scavenging rates of the TP-loaded NGs were 76.5% and 86.1%, respectively. The antitumor activity of the TP-loaded NGs can effectively inhibit the proliferation of HepG₂ cells. Furthermore, TP-loaded NGs were proven to significantly enhance the induction of apoptosis in hepatoma cells and exhibit obvious cell cycle arrest. Our results demonstrate that the Ly–CMC NGs have extensive application prospects as a biocompatible and biodegradable delivery carrier of food functional factors to improve their antitumor effects.

Fabrication of biodegradable TP-loaded Ly and CMC nanogels via self-assembly and the study of their controlled release and absorption process in vivo.     

Design of ferrocenylseleno-dopamine derivatives to optimize the Fenton-like reaction efficiency and antitumor efficacy

In the current study, six ferrocenylseleno-dopamine derivatives with different structural parameters were designed. Among these derivatives, F4b, containing two ferrocene units and a tertiary amine, showed in vitro anticancer activity with IC₅₀ = 2.4 ± 0.4 μM for MGC-803 cells, and its in vivo studies suggested effective antitumor activity in mice bearing an MGC-803 tumor xenograft. Mechanistic study revealed that the cytotoxicity of these ferrocenylseleno-dopamine derivatives is mainly related to the Fenton-like reaction under physiological conditions, and the tertiary amine in F4b can facilitate the H₂O₂ decomposition to generate toxic ˙OH which induces apoptosis through CDK-2 inactivation.

The tertiary amine in F4b facilitates the Fenton-like reaction to generate toxic ˙OH which induces apoptosis through CDK-2 inactivation.     

Low-temperature fluoride-assisted synthesis of mullite whiskers

Mullite is a promising material for advanced ceramic applications. The synthesis of mullite from oxides requires very high temperatures (T > 1000 °C). Here highly crystalline mullite whiskers with an average length and diameter of 2.37 ± 1.7 μm and 0.18 ± 0.11 μm, respectively, were synthesized by a fluoride-assisted method from aluminium sulfate, aluminium fluoride and fumed silica at a temperature as low as 800 °C.

Fluoride-assisted method for obtaining highly crystalline mullite whiskers at low temperature (∼800 °C) is reported.     

TCCA-mediated oxidative rearrangement of tetrahydro-β-carbolines: facile access to spirooxindoles and the total synthesis of (±)-coerulescine and (±)-horsfiline

Multi-reactive centered reagents are beneficial in chemical synthesis due to their advantage of minimal material utilization and formation of less by-products. Trichloroisocyanuric acid (TCCA), a reagent with three reactive centers, was employed in the synthesis of spirooxindoles through the oxidative rearrangement of various N-protected tetrahydro-β-carbolines. In this protocol, low equivalents of TCCA were required to access spirooxindoles (up to 99% yield) with a wide substrate scope. Furthermore, the applicability and robustness of this protocol were proven for the gram-scale total synthesis of natural alkaloids such as (±)-coerulescine (1) and (±)-horsfiline (2) in excellent yields.

Three-reactive centered reagent (TCCA) mediated construction of spirooxindoles through an oxidative rearrangement of various N-protected tetrahydro-β-carbolines and total synthesis of natural alkaloids (±)-coerulescine and (±)-horsfiline.     

Poly(ethylene glycol) brush-b-poly(N-vinylpyrrolidone)-based double hydrophilic block copolymer particles crosslinked via crystalline α-cyclodextrin domains

Self-assembly of block copolymers is a significant area of polymer science. The self-assembly of completely water-soluble block copolymers is of particular interest, albeit a challenging task. In the present work the self-assembly of a linear-brush architecture block copolymer, namely poly(N-vinylpyrrolidone)-b-poly(oligoethylene glycol methacrylate) (PVP-b-POEGMA), in water is studied. Moreover, the assembled structures are crosslinked via α-CD host/guest complexation in a supramolecular way. The crosslinking shifts the equilibrium toward aggregate formation without switching off the dynamic equilibrium of double hydrophilic block copolymer (DHBC). As a consequence, the self-assembly efficiency is improved without extinguishing the unique DHBC self-assembly behavior. In addition, decrosslinking could be induced without a change in concentration by adding a competing complexation agent for α-CD. The self-assembly behavior was followed by DLS measurement, while the presence of the particles could be observed via cryo-TEM before and after crosslinking.

Self-assembly of the double hydrophilic block copolymer poly(N-vinylpyrrolidone)-b-poly(oligoethylene glycol methacrylate) and supramolecular crosslinking via α-cyclodextrin in water is presented.     

Kinetic study on the grain growth of PuO2 nanocrystals

Kinetic measurements on the grain growth of PuO₂ nano-crystals are presented. On the basis of isothermal XRD measurements at temperatures of 820 °C, 900 °C, 1000 °C, and 1100 °C the activation energy for the crystallite growth of PuO₂ nanopowder is determined as 351(5) kJ mol⁻¹ in the temperature range from 820 to 1000 °C. Modelling shows that in this T range growth happens likely through surface diffusion.

Results on the kinetics of PuO₂ nanocrystals are presented in the temperature range below 1100 °C showing the activation energy for the particle growth is ∼350 kJ mol⁻¹. Particle growth proceeds from the nano- to the micrometer scale.     

Multiple 3D-QSAR modeling,e-pharmacophore,molecular docking,and in vitro study to explore novel AChE inhibitors

Ligand-based and energy-optimized structure-based approaches were considered to obtain excellent candidates as AChE inhibitors. The known AChE inhibitors were utilized to develop a pharmacophore hypothesis, HPRRR and X-ray crystallographic structures of AChE were used to produce three e-pharmacophore hypotheses viz. AHHRR, AHRR, and DHRR. Based on in silico approaches, we came across eight structurally diverse hits as non-competitive AChE inhibitors with good ADME properties. The best four hits, ZINC20592007, ZINC05354646, ZINC20649934, and ZINC39154782 were non-toxic, neuroprotective, and were selective AChE inhibitors (IC₅₀ values 482 ± 1.88 nM, 580 ± 1.63 nM, 854 ± 2.65 nM, and 636 ± 1.79 nM respectively). The hits showed non-competitive inhibition of AChE at PAS site with attractive K_i values (0.21 ± 0.027 μM, 0.27 ± 0.064 μM, 0.3 ± 0.018 μM, and 0.28 ± 0.032 μM for ZINC20592007, ZINC05354646, ZINC20649934, and ZINC39154782 respectively), and increased the cholinergic activity as well as inhibited Aβ aggregation.

Ligand-based and energy-optimized structure-based approaches were helpful to obtain excellent candidates as non-toxic, PAS site selective, non-competitive AChE inhibitors.     

Knecorticosanones C–H from the fruits of Knema globularia (Lam.) warb

Six undescribed polyketides, 1–6, were discovered from the fruits of Knema globularia (Lam.) warb. Two known polyketides and three known lignans were also isolated. Cytotoxicities against HepG2 and KKU-M156 cells of all polyketides were evaluated. Compound 1 displayed the most cytotoxic activity against HepG2 and KKU-M156 cell lines with IC₅₀ values of 1.57 ± 0.37 and 1.78 ± 0.14 μg mL⁻¹, respectively. The structure of all isolates was identified using spectroscopic methods including NMR, IR, MS and ECD.

Compound 1 displayed the most cytotoxic activity against HepG2 and KKU-M156 cell lines with IC₅₀ values of 1.57 ± 0.37 and 1.78 ± 0.14 μg mL⁻¹, respectively.     

Fused multicyclic polyketides with a two-spiro-carbon skeleton from mangrove-derived endophytic fungus Epicoccum nigrum SCNU-F0002

A pair of uncommon fused multicyclic polyketides with a two- spiro-carbon skeleton, (±)-isoepicolactone, (±)-1, and one new isobenzofuranone monomer (4), together with four other known biosynthetically related compounds were isolated from the fermentation of an endophytic fungus, Epicoccum nigrum SCNU-F0002, which was isolated from the fresh fruit of the mangrove plant Acanthus ilicifolius L. Comprehensive spectroscopic analysis, X-ray crystallography, together with calculated ECD, were employed to define the structures. The antibacterial and COX-2 inhibitory activities of the compounds (1–6) were evaluated. A possible biogenetic pathway of (±)-isoepicolactone was confirmed.

A pair of uncommon fused multicyclic polyketides, (±)-isoepicolactone and one new isobenzofuranone monomer, together with four other known biosynthetically related compounds were isolated from the fermentation of fungus Epicoccum nigrum SCNU-F0002.     

A mild and metal-free synthesis of 2- and 1-alkyl/aryl/dialkyl-aminoquinolines and isoquinolines

A simple synthetic strategy has been developed for the synthesis of 2- and 1-alkyl/aryl/dialkylaminoquinolines and isoquinolines from the easily available quinoline and isoquinoline-N-oxides, different amines, triflic anhydride as activating agent and acetonitrile as solvent in a one-pot reaction under metal-free conditions at 0 °C to room temperature.

A synthetic strategy has been developed for synthesis of 2 and 1-aminoquinolines and isoquinolines from quinoline and isoquinoline-N-oxides, amines and triflic anhydride in acetonitrile at 0 °C to room temperature.     

Cancer cell membrane-camouflaged MOF nanoparticles for a potent dihydroartemisinin-based hepatocellular carcinoma therapy

Developing new drugs for cancer treatment remains a challenging task. Herein, cancer cell membrane biomimetic ferrous ion-doped metal–organic framework nanoparticles (ZIF-8 nanoparticles) combined with dihydroartemisinin (DHA) have been designed for targeted cancer treatment with low toxicity and side effects. The biomimetic nanomaterials (CDZs) have excellent homologous targeting ability and can accumulate in tumor tissues. In an acid tumor microenvironment, ferrous ions and DHA could be released with the degradation of materials. DHA, an ancient Chinese medicine, combines with ferrous ions to produce a powerful anti-tumor effect. In human liver cancer models, about 90.8% of tumor growth was suppressed. In addition, the nanomaterial has no obvious toxic and side effects in vivo and is a highly effective and low-toxicity anti-tumor drug with a strong clinical application value.

Developing new drugs for cancer treatment remains a challenging task.     

Quercetin spectrofluorometric quantification in aqueous media using different surfactants as fluorescence promoters

Quercetin spectrofluorometric quantification was carried out in aqueous media (pH 7) using micelles of surfactants, namely: CTAB, SDS and TX100 as promoters of quercetin fluorescence, having a critical micelle concentration, CMC, of: 0.94 ± 0.03, 7.7 ± 0.6 and 0.18 ± 0.3 mM, respectively, measured through UV-Vis spectrophotometry. The thermodynamic binding constant, K, for the quercetin-surfactants'' micelles supramolecular complex was estimated to be (log(K/M⁻¹)) = 2.87 ± 0.02, 2.78 ± 0.04 and 2.80 ± 0.04, respectively, from fluorescence spectrophotometry. With the aid of these parameters it was possible to construct species distribution diagrams and choose the experimental conditions where quercetin can be quantified in aqueous media from fluorescence measurements. The best lowest limit of detection (0.244 ± 0.092) μM was achieved with CTAB micelles while the best sensitivity (2.919 ± 0.054) M⁻¹ corresponded to SDS.

Quercetin spectrofluorometric quantification was carried out in aqueous media using micelles of surfactants, namely: CTAB, SDS and TX100 as promoters of quercetin fluorescence and stability.     

Self-assembly of an oligo(p-phenylenevinylene)-based molecule on an HOPG surface: insights from multi-scale simulation and STM observation

To gain knowledge of the most important weak interactions for supramolecular self-assembly and observe molecular structure for self-assembled architectures, the two-dimensional self-assembly of an oligo(p-phenylenevinylene)-based molecule (AS-OPV) on highly oriented pyrolytic graphite has been investigated. Accurate atomic configuration for the AS-OPV self-assembled pattern has been identified by means of multi-scale simulation combined with scanning tunneling microscopy (STM) experiments. The weak interactions which contribute to the formation of AS-OPV self-assembly are studied by analysis of non-covalent interactions existing in the system and theoretical calculation of their energy values. Investigation of the molecular structure of self-assembly and STM images at a certain temperature range is performed by molecular dynamics and density functional theory simulations. This work paves the way to explore the contribution of weak interactions for the self-assembly system, as well as providing a reference to observe the possible self-assembled structure at temperatures not convenient for direct experimental observation.

DFT and MD simulations together with STM investigation were perfomed to study the weak interactions and structural stability of an oligo(p-phenylenevinylene)-based molecule on highly oriented pyrolytic graphite surface at different temperatures.