Discovery of gefitinib-1,2,3-triazole derivatives against lung cancer via inducing apoptosis and inhibiting the colony formation.

A series of 20 novel gefitinib derivatives incorporating the 1,2,3-triazole moiety were designed and synthesized. The synthesized compounds were evaluated for their potential anticancer activity against EGFR wild-type human non-small cell lung cancer cells (NCI-H1299, A549) and human lung adenocarcinoma cells (NCI-H1437) as non-small cell lung cancer. In comparison to gefitinib, Initial biological assessments revealed that several compounds exhibited potent anti-proliferative activity against these cancer cell lines.

Synthesis and In Vitro Antitumor Activity Evaluation of Gefitinib-1,2,3-Triazole Derivatives.

In this study, 14 structurally novel gefitinib-1,2,3-triazole derivatives were synthesized using a click chemistry approach and characterized by H NMR, C NMR and high-resolution mass spectrometry (HRMS). Preliminary cell counting kit-8 results showed that most of the compounds exhibit excellent antitumor activity against epidermal growth factor receptor wild-type lung cancer cells NCI-H1299, A549 and NCI-H1437. Among them, and showed the most prominent inhibitory effects.

Synthesis and activity study of novel N,N-diphenylurea derivatives as IDO1 inhibitors.

Indoleamine 2,3-dioxygenase 1 (IDO1) has attracted much attention in the field of cancer immunotherapy as an immunomodulatory enzyme. To identify potential IDO1 inhibitors, a novel series of compounds with N,N-diphenylurea and triazole structures were synthesized. The designed compounds underwent organic synthesis, and subsequent enzymatic activity experiments targeting IDO1 confirmed their activity at the molecular level.

Bioassay-Guided Isolation of Two Eudesmane Sesquiterpenes from Using Centrifugal Partition Chromatography.

In this study, a centrifugal partition chromatography (CPC) separation was applied to identify antioxidant-responsive element (ARE) induction molecules from the crude extract of roots. CPC was operated with a two-phase solvent system composed of -hexane-methanol-water (10:8.5:1.

Acoustic Mist Ionization-Mass Spectrometry: A Comparison to Conventional High-Throughput Screening and Compound Profiling Platforms.

Drug discovery usually begins with a high-throughput screen (HTS) of thousands to millions of molecules to identify starting points for medicinal chemistry. Conventional HTS platforms require expensive reagents and typically have complex assay formats. HTS platforms based on radioactivity are expensive, both in terms of reagent cost and disposal.

Bioassay-Guided Separation of Using Comprehensive Linear Gradient Centrifugal Partition Chromatography.

A comprehensive linear gradient solvent system for centrifugal partition chromatography (CPC) was developed for the bioassay-guided isolation of natural compounds. The gradient solvent system consisted of three different ternary biphasic solvents types: -hexane-acetonitrile-water (10:2:8, /), ethyl acetate-acetonitrile-water (10:2:8, /), and water-saturated -butanol-acetonitrile-water (10:2:8, /). The lower phase of the -hexane-acetonitrile-water (10:2:8, /) was used as the stationary phase, while its upper phase, as well as ethyl acetate-acetonitrile-water (10:2:8), and water-saturated -butanol-acetonitrile-water (10:2:8, /) were pumped to generate a linear gradient elution, increasing the mobile phase polarity.

Ultrabright Full Color Carbon Dots by Fine-Tuning Crystal Morphology Controllable Synthesis for Multicolor Bioimaging and Sensing.

In this paper, two kinds of novel carbon nanocrystals (CNCs) with different crystal morphologies (the branch-chain young sprout form (CM1) and conifer-pine form (CM2)) were obtained in a controllable way. The mechanism of crystal morphological development was explored well. When the two kinds of the CNCs were dissolved in different polar solvents, they voluntarily become "ultrafine crystals" at the moment.

Author Correction: Prioritizing multiple therapeutic targets in parallel using automated DNA-encoded library screening.

This corrects the article DOI: 10.1038/ncomms16081.

Bioactive Asarone-Derived Phenylpropanoids from the Rhizome of Acorus tatarinowii Schott.

Eight new (1a/1b, 2a, 3a, 4a/4b, and 5a/5b) and seven known (2b, 3b, and 6-10) asarone-derived phenylpropanoids, a known asarone-derived lignan (12), and four known lignan analogues (11 and 13-15) were isolated from the rhizome of Acorus tatarinowii Schott. The structures were elucidated via comprehensive spectroscopic analyses, modified Mosher's method, and quantum chemical calculations. Compounds 1-8 were present as enantiomers, and 1-5 were successfully resolved via chiral-phase HPLC.

[Progress of gene editing technologies and prospect in traditional Chinese medicine].

Gene editing is a kind of technologies that makes precise modification to the genome. It can be used to knock out/in and replace the specific DNA fragment, and make accurate gene editing on the genome level. The essence of the technique is the DNA sequence change with use of non homologous end link repair and homologous recombination repair, combined with specific DNA target recognition and endonuclease.

Chiral resolution, absolute configuration, and bioactivity of a new racemic asarone derivative from the rhizome of Acorus tatarinowii.

A new asarone-derived racemate (1) was isolated from the rhizome of Acorus tatarinowii. The structure of 1 was established by comprehensive spectroscopic analyses, and it was successfully resolved by chiral HPLC, demonstrating that it is racemic. The absolute configurations of 1a [(-)-acortatarone A] and 1b [(+)-acortatarone A] were determined using quantum chemical calculations.

Prioritizing multiple therapeutic targets in parallel using automated DNA-encoded library screening.

The identification and prioritization of chemically tractable therapeutic targets is a significant challenge in the discovery of new medicines. We have developed a novel method that rapidly screens multiple proteins in parallel using DNA-encoded library technology (ELT). Initial efforts were focused on the efficient discovery of antibacterial leads against 119 targets from Acinetobacter baumannii and Staphylococcus aureus.

[Effects of combination of glycyrrhizin acid, ligustrazine and puerarin on LPS-induced cytokines expression in macrophage].

To study the anti-inflammatory activity of glycyrrhizin acid, ligustrazine and puerarin. In the study, the liquichip-based high-throughput synchronous detection technique for 23 inflammatory factors, uniform design, comprehensive weight method were adopted to study the effect of different combined administration of glycyrrhizin acid, ligustrazine and puerarin in inhibiting the expression of lipopolysaccharide (LPS)-induced RAW264. 7 cells and multiple inflammatory cytokines.

New IDH1 mutant inhibitors for treatment of acute myeloid leukemia.

Neomorphic mutations in isocitrate dehydrogenase 1 (IDH1) are driver mutations in acute myeloid leukemia (AML) and other cancers. We report the development of new allosteric inhibitors of mutant IDH1. Crystallographic and biochemical results demonstrated that compounds of this chemical series bind to an allosteric site and lock the enzyme in a catalytically inactive conformation, thereby enabling inhibition of different clinically relevant IDH1 mutants.

[Effects of glycyrrhizin acid and licorice flavonoids on LPS-induced cytokines expression in macrophage].

Glycyrrhizin acid and licorice flavonoids are the component of Glycyrrhiza uralensis Fisch root that has been used for various medicinal purposes in traditional oriental medicine for thousands of years. Macrophages as a principal component of immune system play an important role in the initiation, modulation and final activation of immune response against pathogens. In the present study, glycyrrhizin acid and licorice flavonoids was investigated the anti-inflammatory effect on lipopolysaccharide (LPS)-induced macrophage cell line of RAW264.

Detection of survivin-expressing circulating cancer cells in the peripheral blood of patients with esophageal squamous cell carcinoma and its clinical significance.

We previously demonstrated that the detection of circulating cancer cells (CCC) expressing survivin mRNA could provide valuable information for predicting recurrence in patients with breast, lung, gastric and colorectal carcinoma. The purpose of this study is to investigate whether the detection of survivin-expressing CCC in the peripheral blood is also useful for predicting recurrence in patients with esophageal squamous cell carcinoma (ESCC). Blood samples obtained from 108 ESCC patients and 75 healthy volunteers were quantitatively investigated by a technique that detected reverse transcription-polymerase chain reaction products based on a hybridization-enzyme linked immunosorbent essay.

Detection of survivin-expressing circulating cancer cells (CCCs) in peripheral blood of patients with gastric and colorectal cancer reveals high risks of relapse.

Background: We previously demonstrated that the detection of circulating cancer cells (CCCs) expressing survivin mRNA could provide valuable information for predicting metastasis and recurrence in breast cancer. The objective of this study was to investigate whether or not the detection of survivin expression in the peripheral blood could also have significant effects on the clinical outcomes of patients with gastric and colorectal cancer.

Methods: Survivin-expressing CCCs in peripheral blood samples obtained from 55 gastric cancer patients, 86 colorectal cancer patients, and 87 healthy volunteers were quantitatively examined by using a RT-PCR ELISA.

Clinical significance of detecting survivin-expressing circulating cancer cells in patients with non-small cell lung cancer.

We previously demonstrated that the detection of circulating cancer cells (CCC) expressing survivin mRNA could provide valuable information for predicting metastasis and recurrence in breast cancer. The objective of this study was to investigate the significance of detecting survivin-expressing CCC on the clinical outcomes of patients with non-small cell lung cancer (NSCLC). Peripheral blood samples collected from 143 NSCLC patients and 177 healthy volunteers were quantitatively evaluated using a technique developed in our laboratory that detected reverse transcription-polymerase chain reaction (RT-PCR) products based on a hybridisation-enzyme linked immunosorbant essay (ELISA), which we called RT-PCR ELISA.

Thiol-based angiotensin-converting enzyme 2 inhibitors: P1 modifications for the exploration of the S1 subsite.

Screening of a metalloprotease library led to the identification of a thiol-based dual ACE/NEP inhibitor as a potent ACE2 inhibitor. Modifications of the P(1) benzyl moiety led to improvements in ACE2 potency as well as to increased selectivity versus ACE and NEP.

1,4-Diphenyl-1,4-di-4-pyridyl-2,3-diaza-1,3-butadiene: weak C-H...N and C-H...pi hydrogen bonds.

In the title compound, C24H18N4, each Schiff base molecule is centrosymmetric and interacts with four neighbours via four C-H(Ph)...

C-terminal CTII motif of 2',3'-cyclic nucleotide 3'-phosphodiesterase undergoes carboxylmethylation.

Eukaryotic proteins with a carboxyl-terminal CaaX motif are modified by isoprenylation and subsequently processed by proteolysis of the three terminal amino acids and carboxylmethylation of the exposed cysteine residue. The myelination-associated 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) has a C-terminal CTII sequence and is isoprenylated; however, no examples of subsequent processing exist when threonine, a polar residue, is located adjacent to the cysteine. Here we show that CNP is capable of being carboxylmethylated in both insect cells and glioma cells.

Purification and partial characterization of a cell adhesion molecule (gp150) involved in postaggregation stage cell-cell binding in Dictyostelium discoideum.

A cell surface glycoprotein of apparent Mr 150,000 (gp150) has been implicated in mediating EDTA-resistant cell-cell adhesion in Dictyostelium discoideum. A simple purification scheme making use of high-performance liquid chromatography has been devised to purify gp150 to near homogeneity. Purified gp150 was capable of neutralizing the effect of a rabbit antiserum raised against gel-purified gp150, which was previously reported to be a potent inhibitor of cell-cell adhesion (Geltosky, J.