Effect of Chemical Treatment of Cotton Stalk Fibers on the Mechanical and Thermal Properties of PLA/PP Blended Composites.

Different chemical treatment methods were employed to modify the surface of cotton stalk fibers, which were then utilized as fillers in composite materials. These treated fibers were incorporated into polylactic acid/polypropylene melt blends using the melt blending technique. Results indicated that increasing the surface roughness of cotton stalk fibers could enhance the overall mechanical properties of the composite materials, albeit potentially leading to poor fiber-matrix compatibility. Conversely, a smooth fiber surface was found to improve compatibility with polylactic acid, while Si-O-C silane coating increased fiber regularity and interfacial interaction with the matrix, thereby enhancing heat resistance. The mechanical properties and thermal stability of the composite materials made from alkali/silane-treated fibers exhibited the most significant improvement. Furthermore, better dispersion of fibers in the matrix and more regular fiber orientation were conducive to increasing the overall crystallinity of the composite materials. However, such fiber distribution was not favorable for enhancing impact resistance, although this drawback could be mitigated by increasing the surface roughness of the reinforcing fibers.

A novel [1, 2, 4]triazolo[5,1-b]quinazoline derivative as a fluorescent probe for highly selective detection of Fe3+ ions.

A novel [1, 2, 4]triazolo[5,1-b]quinazoline fluorescent probe (VIi) for Fe3+ was developed, featuring with rapid response (< 5 s) and specific selectivity to Fe3+, low detection limit (1.3 × 10-5 M), as well as the ability to resist interference of chelating agent (e.g. EDTA). VIi-based fluorescent test paper can quickly recognize Fe3+ under irradiation at the wavelength of 365 nm. The fluorescence probe VIi has potential application prospects for the detection of Fe3+ in real circumstance.

Design, synthesis and SAR of novel 7-azaindole derivatives as potential Erk5 kinase inhibitor with anticancer activity.

The extracellular signal-regulated kinase 5 (Erk5) signaling plays a crucial role in cancer, and regulating its activity may have potential in cancer chemotherapy. In this study, a series of novel 7-azaindole derivatives (4a-5o) were designed and synthesized. Their antitumor activities on human lung cancer A549 cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, 4',6-diamidino-2-phenylindole (DAPI) staining and colony formation assay. Among them, compounds 4a, 4 h, 5d and 5j exhibited good anti-proliferative activity with the IC50 values of 6.23 µg/mL, 8.52 µg/mL, 7.33 µg/mL and 4.56 µg/mL, respectively, equivalent to Erk5 positive control XMD8-92 (IC50 = 5.36 µg/mL). The results of structure-activity relationships (SAR) showed that double bond on the piperidine ring and N atoms at the N7 position of 7-azaindole was essential for their antiproliferative activity. Furthermore, compounds 4a and 5j exhibited good inhibition on Erk5 kinase through Western blot analysis and possible action site of compounds with Erk5 kinase was elucidated by molecular docking.

A New Pathway for the Synthesis of Ketones from Aldehydes and Sulfonylhydrazones: Is Diazo the Key Intermediate?

A new pathway via a cyclic intermediate for the synthesis of ketones from aldehydes and sulfonylhydrazone derivatives under basic conditions is proposed. Several control experiments were performed along with analysis of the mass spectra and in-situ IR spectra of the reaction mixture. Inspired by the new mechanism, an efficient and scalable method for homologation of aldehydes to ketones was developed. A wide variety of target ketones were obtained in yields of 42-95 % by simply heating the 3-(trifluoromethyl)benzene sulfonylhydrazones (3-(Tfsyl)hydrazone) for 2 h at 110 °C with aldehydes and with K2 CO3 and DMSO as base and solvent, respectively.

Design, synthesis, anticonvulsant activity and structure-activity relationships of novel 7-Azaindole derivatives.

In search of new-structure compounds with good anticonvulsant activity and low neurotoxicity, a series of 3-(1,2,3,6-tetrahydropyridine)-7-azaindole derivatives was designed and synthesized. Their anticonvulsant activities were evaluated by maximal electroshock (MES) and pentylenetetrazole (PTZ) test, and neurotoxicity was determined by the rotary rod method. In the PTZ-induced epilepsy model, compounds 4i, 4p and 5 k showed significant anticonvulsant activities with ED50 values at 30.55 mg/kg, 19.72 mg/kg and 25.46 mg/kg, respectively. However, these compounds did not show any anticonvulsant activity in the MES model. More importantly, these compounds have lower neurotoxicity with protective index (PI = TD50/ED50) values at 8.58, 10.29 and 7.41, respectively. In order to obtain a clearer structure-activity relationship, more compounds were designed rationally based on 4i, 4p and 5 k and their anticonvulsant activities were evaluated on PTZ models. The results demonstrated that the N-atom at the 7-position of the 7-azaindole and the double-bond in the 1,2,3,6-tetrahydropyridine skeleton was essential for antiepileptic activities.

Synthesis of 19-hydroxyprogesterone and insights into the ring-opening mechanism of the 6,19-epoxy bridge.

An efficient and scalable process for the synthesis of 19-hydroxyprogesterone was obtained through seven steps with 34.5% total yield, which is much higher than the process reported in the literature (11.0% total yield). The plausible ring-opening mechanism of 6,19-epoxy bridge in compound 7 was first proposed and the structures of intermediates were supported by the LC-MS analysis of the reaction mixture.

Discovery of 7-alkyloxy- [1,2,4] triazolo[1,5-a] pyrimidine derivatives as selective positive modulators of GABAA1 and GABAA4 receptors with potent antiepileptic activity.

A series of 7-alkoxy - [1,2,4] triazolo [1, 5-a] pyrimidine derivatives were designed and synthesized. Maximal electroshock (MES) and pentylenetetrazole (PTZ) tests were utilized to access their anticonvulsant activity. Most of the series of compounds exhibited significant anti-seizure effects. Further studies demonstrated that the anticonvulsant activity of these compounds mainly depended on their allosteric potentiation of GABAA receptors. Among them, compound 10c was picked for the mechanism study due to its potent activity. The compound is more sensitive to subunit configurations of synaptic α1ß2γ2 and extrasynaptic α4ß3δ GABAA receptors, but there were no effects on NMDA receptors and Nav1.2 sodium channels. Meanwhile, 10c acted on the sites of GABAA receptors distinct from commonly used anticonvulsants benzodiazepines and barbiturates. Furthermore, studies from native neurons demonstrated that compound 10c also potentiated the activity of native GABAA receptors and reduced action potential firings in cultured cortical neurons. Such structural compounds may lay a foundation for further designing novel antiepileptic molecules.

A novel [1,2,4]triazolo[1,5-a]pyrimidine derivative as a fluorescence probe for specific detection of Fe3+ ions and application in cell imaging.

The detection of metal ions is of particular importance for monitoring environmental pollution and life metabolic activities. However, it is still a challenge to achieve Fe3+ detection with specific sensitivity and rapid response, especially in the presence of chelating agents for Fe3+ ions. Herein, a novel fluorescence probe for Fe3+, i.e., amide derivative of [1,2,4]triazolo[1,5-a] pyrimidine (TP, Id), was synthesized, featuring specific Fe3+ selectivity, rapid quenching (5 s), low limit of detection (0.82 µM), good permeability and low cytotoxicity. More importantly, Id can be used to identify and detect Fe3+ in the presence of existing strong chelating agents (e.g., EDTA) for Fe3+ ions. The results show that the as-synthesized fluorescence probe is particularly suitable as a bioimaging reagent to monitor intracellular Fe3+ in living HeLa cells. Furthermore, we proposed the binding mode for Id with Fe3+ ions and the light-emitting mechanism through high-resolution mass spectra and density function theory calculations, respectively. An Id-based test paper can be used to rapidly identify Fe3+. These results are expected to improve the development of new sensitive and specific fluorescent sensors for Fe3+.

Surfactant cocamide monoethanolamide causes eye irritation by activating nociceptor TRPV1 channels.

BACKGROUND AND PURPOSE: Cocamide monoethanolamide (CMEA) is commonly used as a surfactant-foam booster in cosmetic formulations. Upon contact with the eye or other sensitive skin areas, CMEA elicits stinging and lasting irritation. We hypothesized a specific molecular interaction with TRPV1 channels by which CMEA caused eye irritation. EXPERIMENTAL APPROACH: Eye irritancy was evaluated using eye-wiping tests in rabbits and mice. Intracellular Ca2+ concentrations and action potentials were measured using Ca2+ imaging and current clamp respectively. Voltage clamp, site-direct mutagenesis and molecular modelling were used to identify binding pockets for CMEA on TRPV1 channels. KEY RESULTS: CMEA-induced eye irritation is ameliorated by selective ablation of TRPV1 channels.Rodents exhibit much stronger responses to CMEA than rabbits. In trigeminal ganglion neurons, CMEA induced Ca2+ influx and neuronal excitability, effects mitigated by a TRPV1 channel inhibition and absent in TRPV1 knockout neurons. In HEK-293 cells expressing TRPV1 channels, CMEA increased whole-cell currents by increasing channel open probability (EC50 = 10.2 µM), without affecting TRPV2, TRPV3, TRPV4, and TRPA1 channel activities. Lauric acid monoethanolamide (LAMEA), the most abundant constituent of CMEA, was the most efficacious and potent TRPV1 channel activator, binding to the capsaicin-binding pocket of the channel. The T550I mutants of rabbit and human TRPV1 channels exhibit much lower sensitivity to LAMEA. CONCLUSIONS AND IMPLICATION: CMEA directly activates TRPV1 channels to produce eye irritation. Rabbits, the standard animal used for eye irritancy tests are poor models for evaluating human eye irritants structurally related to CMEA. Our study identifies potential alternatives to CMEA as non-irritating surfactants.

The importance of indole and azaindole scaffold in the development of antitumor agents.

With some indoles and azaindoles being successfully developed as anticancer drugs, the design and synthesis of indole and azaindole derivatives with remarkable antitumor activity has received increasing attention and significant progress has been made. This paper reviews the recent progress in the study of tumorigenesis, mechanism of actions and structure activity relationships about anticancer indole and azindole derivatives. Combining structure activity relationships and molecular targets-related knowledge, this review will help researchers design more effective, safe and cost-effective anticancer indoles and azindoles agents.

Discovery of [1,2,4]-triazolo [1,5-a]pyrimidine-7(4H)-one derivatives as positive modulators of GABAA1 receptor with potent anticonvulsant activity and low toxicity.

In searching for more effective and safer antiepileptic drugs, a series of 2,5-disubstituted [1,2,4]-triazolo[1,5-a]pyrimidine-7(4H)-one derivatives were designed and synthesized. Spontaneous Ca2+ oscillations (SCOs) of cortical neurons were used for in vitro phenotypic screening. Maximal electroshock test (MES) and pentylenetetrazole (PTZ) test were used to access their anticonvulsant activity, and rotarod test was used to estimate their neurotoxicity. The active compounds in in vitro model are specifically effective in pentylenetetrazole (PTZ)-induced epilepsy model but not maximal electroshock (MES) model, more importantly with lower neurotoxicity as compared to commonly used drugs. Among them, compound 5c and 5e showed significant anticonvulsant activities in PTZ-induced epilepsy model with ED50 values at 31.81 mg/kg and 40.95 mg/kg, respectively. These compounds have improved neurotoxicity with protective index (PI = TD50/ED50) values at 17.22 and 9.09, respectively. Finally we demonstrated that compound 5c and 5e mainly acted on GABAA receptor as positive modulators but not sodium channels. Thus the present study has provided potential candidates for further investigation in epilepsy.

Synthesis and in vitro anti-epileptic activities of novel [1,2,4]-triazolo[1,5-a]pyrimidin-7(4H)-one derivatives.

In this investigation, eight novel 2,5-disubstituted [1,2,4]-triazolo[1,5-a]pyrimidin-7(4H)-one and eight novel 2,5-disubstituted [1,2,4]-triazolo[1,5-a]pyrimidine amine derivatives were synthesized based on the novel marine natural product Essramycin. Their anti-epileptic activities were evaluated by 4-aminopyridine (4-AP)-induced hyper excitability model in primary cultured neocortical neurons. Five compounds with [1,2,4]-triazolo[1,5-a]pyrimidin-7(4H)-one skeleton showed remarkable anti-epileptic activities. The preliminary structure-activity relationship (SAR) showed that the pyrimidine-7(4H)-one motif is the necessary "active core" of anti-epileptic activity. To understand the action mechanism of anti-epileptic activity of [1,2,4]-triazolo[1,5-a]pyrimidin-7(4H)-one compounds, docking studies using the model of GABAA as docking scaffolds were performed and the docking results were in concordance with the experiment observations. [Formula: see text].

Direct amidation of non-activated phenylacetic acid and benzylamine derivatives catalysed by NiCl2.

This paper describes an eco-friendly and efficient direct amidation of benzylamine and phenylacetic acid derivatives in the presence of 10 mol% NiCl2 as catalyst without any drying agent. For the different phenylacetic acid and benzylamine derivatives, the direct catalysed amidation gave moderate-to-excellent yields in toluene. The steric and electronic effects of substituent groups on the phenyl ring of acid were crucial to the yields of the direct amidation. The catalyst NiCl2 can be recycled three times without loss of activity.

Synthetic Strategy and Anti-Tumor Activities of Macrocyclic Scaffolds Based on 4-Hydroxyproline.

A series of novel 13- to 15-member hydroxyproline-based macrocycles, which contain alkyl-alkyl ether and alkyl-aryl ether moieties, have been synthesized by the strategy of macrocyclization utilising azide-alkyne cycloaddition, Mitsunobu protocol and amide formation. Their anti-tumor activities towards A549, MDA-MB-231 and Hep G2 cells were screened in vitro by an MTT assay. The results indicated that 13-member macrocycle 33 containing alkene chain showed the best results, exhibiting the highest inhibitory effects towards lung cancer cell line A549, which was higher than that of the reference cisplatin (IC50 value = 2.55 µmol/L).

[Chemical constituents of Uvaria kurzii].

OBJECTIVE: To investigate the chemical constituents of the branches and leaves of (Jvariu kurzii. METHOD: Compounds were isolated and purified by silica gel and Sephadex LH-20 column chromatography. Their chemical structures were identified on the basis of physicoc hemical properties and spectral data. RESULT: Nineteen compounds were isolated and identified as: beta-sitosterol hexadecanoate (1), stigmasterol hexadecanoate (2), beta-acetylsitosterol (3), beta-acetylstigmasterul (4), tetratriacontanol (5), dotriacontanoic acid (6), beta-sitosterol (7), stigmasterol (8), 5alpha-stigmast-3 , 6-dione (9) , 5alpha-stigmast-22-ene-3,6-dione (10), vanillic acid (11), protocatechuic acid (12), N-(p-trans-collmaroyl) tyramine (13). kaempferol-3-O-beta-D-(6"-O-p-coumaryoyl) galactopyraunoside (14), kaempferol-3-O-rutinoide (15), rutin (16), daucosterol (17), L-quebrachitol (18), allantoin (19), respectively. CONCLUSION: Compounds 1-6, 9, 10, 13, 18, 19 were isolated from Annonaceac plants; Compounds 14-16 were obtained from the gemis Uvaria; an 7, 8, 11, 12, 17 were separated from this plant respectively for the first time.

The synthesis of analogs of shuangkangsu, a novel natural cycloperoxide glucoside from Lonicera japonica Thunb.

Four novel optically pure cycloperoxide glucosides 9a, 9b, 10a, and 10b, analogs of shuangkangsu--a natural product with unusual skeleton and antivirus activity from the buds of Lonicera japonica Thunb, were firstly synthesized by employing peroxidation and glucosidation reactions from phthalaldehyde or 4,5-dichloro phthalaldehyde and glucose.

The structure and absolute configuration of Shuangkangsu: a novel natural cyclic peroxide from Lonicera japonica (Thunb.).

A novel cyclic peroxide, shuangkangsu (1), has been obtained from the water extract of the buds of Lonicera japonica (Thunb.). The structure was elucidated as 5,8-divinyl-1,4-dihydro-1,4-di-O-beta-d-glucopyranosyl-2,3-dioxane (1) on the basis of the spectral data. Its absolute stereochemistry was determined to be (1S, 4S) by comparison of its CD curves with those of its optically pure analogs 2 and 3, which were synthesized from the phthalaldehyde. The absolute configurations of 2 and 3 were determined to be (1R, 4R) and (1S, 4S) by X-ray analysis and CD spectra, respectively. Compound 1 showed significant antiviral activities against influenza virus in chicken embryo and respiratory syncytial virus in cells.