Novel piperazine-1,2,3-triazole leads for the potential treatment of pancreatic cancer.

From lead 1, (-(4-((4-(3-(4-(3-methoxyphenyl)-1-1,2,3-triazol-1-yl)propyl)piperazin-1-yl)sulfonyl)-phenyl)acetamide), a S100A2-p53 protein-protein interaction inhibitor based on an modelling driven hypothesis, four focused libraries were designed and synthesised. Growth inhibition screening was performed against 16 human cancer cell lines including the pancreatic cell lines MiaPaCa2, BxPC3, AsPC-1, Capan-2, HPAC, PANC-1 and the drug resistant CFPAC1. Modification of 1's phenylacetamide moiety, gave with only modest pancreatic cancer activity.

Novel application potential of cinaciguat in the treatment of mixed hyperlipidemia through targeting PTL/NPC1L1 and alleviating intestinal microbiota dysbiosis and metabolic disorders.

Mixed hyperlipidemia, characterized by high levels of triglycerides and cholesterol, is a key risk factor leading to atherosclerosis and other cardiovascular diseases. Existing clinical drugs usually only work on a single indicator, decreasing either triglyceride or cholesterol levels. Developing dual-acting agents that reduce both triglycerides and cholesterol remains a great challenge.

Graph Neural Network-Based Efficient Subgraph Embedding Method for Link Prediction in Mobile Edge Computing.

Link prediction is critical to completing the missing links in a network or to predicting the generation of new links according to current network structure information, which is vital for analyzing the evolution of a network, such as the logical architecture construction of MEC (mobile edge computing) routing links of a 5G/6G access network. Link prediction can provide throughput guidance for MEC and select appropriate c nodes through the MEC routing links of 5G/6G access networks. Traditional link prediction algorithms are always based on node similarity, which needs predefined similarity functions, is highly hypothetical and can only be applied to specific network structures without generality.

ARHGAP9 inhibits colorectal cancer cell proliferation, invasion and EMT via targeting PI3K/AKT/mTOR signaling pathway.

Aim: In digestive system, colorectal cancer (CRC) is a common malignant tumor. The phosphatidylinositol 3-kinase/protein kinase-B/mammalian target of the rapamycin (PI3K/AKT/mTOR) signaling pathway plays a central role in CRC, and the aberrant activation of this pathway is associated with tumorigenesis. We aimed to explore the role of Rho GTPase activating protein 9 (ARHGAP9) in the progression of CRC as well as its regulatory effects on the PI3K/AKT/mTOR pathway.

Hsa_circ_0006732 regulates colorectal cancer cell proliferation, invasion and EMT by miR-127-5p/RAB3D axis.

Colorectal cancer (CRC) remains a malignancy tumor with high metastasis and poor prognosis. We aimed to explore the effect of circular RNA (circRNA) hsa_circ_0006732 in the progression of CRC. Hsa_circ_0006732 expression in CRC tissues and cell lines were detected using qRT-PCR.

Inhibition of long noncoding RNA cancer susceptibility candidate 7 attenuates hepatocellular carcinoma development by targeting microRNA-30a-5p.

Long non-coding RNA (lncRNA) cancer susceptibility candidate 7 (CASC7) was reported to be participated in tumor development. This study was carried out to investigate the functions of CASC7 in hepatocellular carcinoma (HCC) progression. The expression of CASC7 and microRNA-30a-5p (miR-30a-5p) in HCC tissues and cells were detected by quantitative Real-time PCR (qRT-PCR).

3,5-Bis(trifluoromethyl)phenylsulfonamides, a novel pancreatic cancer active lead. Investigation of the terminal aromatic moiety.

Virtual screening identified N-(6-((4-bromobenzyl)amino)hexyl)-3,5-bis(trifluoromethyl)benzenesulfonamide (1) a lead compound that bound to the S100A2-p53 binding groove. S100A2 is a Ca binding protein with implications in cell signaling and is known to be upregulated in pancreatic cancer. It is a validated pancreatic cancer drug target.

Zinc Promotes Microglial Autophagy Through NLRP3 Inflammasome Inactivation via XIST/miR-374a-5p Axis in Spinal Cord Injury.

Zinc has reported to play a neuroprotective role in the development of spinal cord injury (SCI). The protective mechanism of zinc remains to be uncovered. The aim of the current study was to investigate the neuroprotective mechanism of zinc in the progression of SCI.

Separation of three chromones from Saposhnikovia divaricata using macroporous resins followed by preparative high-performance liquid chromatography.

Prim-O-glucosylcimifugin, cimifugin, and 5-O-methylvisamminoside are three major chromone derivatives of Saposhnikovia divaricata that have many pharmacological activities, such as anti-inflammatory and antitumor activities. In the present work, an effective method for the simultaneous separation of prim-O-glucosylcimifugin, cimifugin, and 5-O-methylvisamminoside with high purities was established using HPD-300 resin coupled with preparative high-performance liquid chromatography. The adsorption kinetics curves of the three compounds on the HPD-300 resin were studied and found to fit well according to the pseudo-second-order equation.

Cytotoxic 1,2,3-Triazoles as Potential Leads Targeting the S100A2-p53 Complex: Synthesis and Cytotoxicity.

In silico screening predicted 1 (N-(4-((4-(3-(4-(3-methoxyphenyl)-1H-1,2,3-triazol-1-yl)propyl)piperazin-1-yl) sulfonyl)-phenyl)acetamide) as an inhibitor of the S100A2-p53 protein-protein interaction. S100A2 is a validated pancreatic cancer drug target. In the MiaPaCa-2 pancreatic cell line, 1 was a ∼50 μM growth inhibitor.

Targeting the S100A2-p53 Interaction with a Series of 3,5-Bis(trifluoromethyl)benzene Sulfonamides: Synthesis and Cytotoxicity.

In silico approaches identified 1, N-(6-((4-bromo- benzyl)amino)hexyl)-3,5-bis(trifluoromethyl)benzene sulfonamide, as a potential inhibitor of the S100A2-p53 protein-protein interaction, a validated pancreatic cancer drug target. Subsequent cytotoxicity screening revealed it to be a 2.97 μM cell growth inhibitor of the MiaPaCa-2 pancreatic cell line.

Small molecule inhibitors in pancreatic cancer.

Pancreatic cancer (PC), with a 5 year survival of <7%, is one of the most fatal of all human cancers. The highly aggressive and metastatic character of this disease poses a challenge that current therapies are failing, despite significant efforts, to meet. This review examines the current status of the 35 small molecule inhibitors targeting pancreatic cancer in clinical trials and the >50 currently under investigation.

The Impact of microRNA Regulation on Immune Recovery in HIV-1-Infected Patients Treated during Acute Infection: A Pilot Study.

microRNAs (miRNAs) are small noncoding RNAs involved in a large range of cellular activities and can be used as biomarkers and indicators for diagnosis. We investigated the alterations in miRNA profiles in immune reconstituted vs. nonimmune reconstituted HIV-1-infected individuals to assess the association between miRNAs and the occurrence of immunological nonresponses, with the aim of searching for miRNA-based biomarkers for these HIV-1-infected individuals.

Quaternary ammonium salts substituted by 5-phenyl-1,3,4-oxadiazole-2-thiol as novel antibacterial agents with low cytotoxicity.

Twenty-one novel 5-phenyl-1,3,4-oxadiazole-2-thiol (POT) substituted N-hydroxyethyl quaternary ammonium salts (6a-g, 7a-g, 8a-g) were prepared and characterized by FTIR, NMR, and elemental analysis. Compounds 6a, 6c, and 8a were confirmed by X-ray single-crystal diffraction. They display the unsurpassed antibacterial activity against Staphylococcus aureus, α-H-tococcus, Escherichia coli, P.

Synthesis, Antiproliferative, and Multidrug Resistance Reversal Activities of Heterocyclic α,β-Unsaturated Carbonyl Compounds.

A series of heterocyclic α,β-unsaturated carbonyl compounds (1a-1d, 2a-2d, 3a-3d, 4a-3d, and 5a-5d) with 1,5-diaryl-3-oxo-1,4-pentadienyl pharmacophore were synthesized for the development of anticancer and multidrug resistance reverting agents. The antiproliferative activities were tested against nine human cancer cell lines. Approximately 73% of the IC50 values were below 5 μm, while 35% of these figures were submicromolar, and compounds 3a-3d with 4-trifluoro methyl in the arylidene benzene rings were the most potent, since their IC50 values are between 0.

New sesquiterpenes from the rhizomes of homalomena occulta.

Six new sesquiterpenes (1-6), along with eight known ones (7-14) were isolated from the rhizomes of Homalomena occulta. Structure elucidation of the new compounds was achieved through 1D NMR, 2D NMR spectroscopic techniques and HRESIMS, while the absolute configurations of compounds 1, 2 and 5 were confirmed by X-ray crystallographic analysis. All of the isolates were evaluated for their activity against LPS-induced production of nitrogen oxide (NO) in macrophage cells, and compounds 1 and 5 showed inhibitory effect on NO production with the IC50 values of 21.

Non-toxic O-quaternized chitosan materials with better water solubility and antimicrobial function.

Five water-soluble O-quaternary ammonium salt-chitosans (QAS-CS) bearing N-methyl-N-R-N, N-bis(2-hydroxyethyl) ammonium bromides (R=-benzyl (chloride, BNQAS-CS), -dodecyl (C12QAS-CS), -tetradecyl (C14QAS-CS), -hexadecyl (C16QAS-CS), -octadecyl (C18QAS-CS)) were prepared, respectively. They were characterized by FTIR, (1)H NMR and elemental analysis. Through chemical modification of O-quaternized chitosans, the water solubility of all QAS-CS was improved distinctly.

Synthesis, antitumor activity evaluation of some new N-aroyl-α,β-unsaturated piperidones with fluorescence.

Novel N-aroyl-α,β-unsaturated piperidones, series 1, series 2 and series 3 (featuring 2-bromo-4,5-dimethoxybenzylidene, 4-dimethylaminobenzylidene and 4-trifluoromethylbenzylidene, respectively), were synthesized as candidate cytotoxins. Most of the compounds displayed potent cytotoxicity against the human neoplastic cell lines SK-BR-3, PG-BE1, NCI-H460, MIA PaCa-2 and SW1990 in vitro, and approximately 64% of the IC50 values were lower than 5 μM. Among those tested, compound 1b of series 1, 3a, 3d and 3e of series 3 proved to be the most active.

Rhein prevents endotoxin-induced acute kidney injury by inhibiting NF-κB activities.

This study aimed to explore the effect and mechanisms of rhein on sepsis-induced acute kidney injury by injecting lipopolysaccharide (LPS) and cecal ligation and puncture (CLP) in vivo, and on LPS-induced HK-2 cells in vitro. For histopathological analysis, rhein effectively attenuated the severity of renal injury. Rhein could significantly decrease concentration of BUN and SCr and level of TNF-α and IL-1β in two different mouse models of experimental sepsis.

[Anthraquinones and triterpenoids from roots of Knoxia roxburghii].

Nine compounds were isolated from an ethanol extract of the roots of K. roxburghii by using a combination of various chromatographic techniques including column chromatography over silica gel, MCI gel, Sephadex LH-20, and reversed-phase HPLC. On the basis of physical-chemical properties and spectroscopic data analysis, their structures were identified as munjistin (1), 1-methoxy-3,6-dihydroxy-2-hydroxymethyl-9,10-anthraquinone (2), 1,2,3-trihydroxy-9,10-anthraquinone (3), arjunolic acid (4), hyptatic acid-A (5), hyptatic acid-B (6), 2α,3β,24-trihydroxyurs-12-en-28-oic acid (7), 2α,3β,23-trihydroxyurs-12-en-28-oic acid (8), and daucosterol (9).

Synthesis, characterization and antibacterial properties of dihydroxy quaternary ammonium salts with long chain alkyl bromides.

Five N-methyl-N-R-N,N-bis(2-hydroxyethyl) ammonium bromides (R = -benzyl (chloride, BNQAS), -dodecyl (C12QAS), -tetradecyl (C14QAS), -hexadecyl (C16QAS), -octadecyl (C18QAS)) were prepared based on N-methyldiethanolamine (MDEA) and halohydrocarbon. Five QAS were characterized by FTIR, NMR, and MS. BNQAS, C12QAS, C14QAS, and C16QAS were confirmed by X-ray single-crystal diffraction.

Design, synthesis and bioevaluation of novel N-substituted-3,5-bis(arylidene)-4-piperidone derivatives as cytotoxic and antitumor agents with fluorescent properties.

Ten new N-substituted-3,5-bis(arylidene)-4-piperidone derivatives (series 1 and 2) were synthesized and subsequently evaluated against human carcinoma cell lines SW1990, MIA PaCa-2, PG-BE1, NCI-H460, and SK-BR-3 for cytotoxic activity by the CCK-8 method, and their fluorescent properties were investigated as well. The compounds were confirmed to display greater cytotoxic activity to the neoplastic cells, and approximately 50% of the IC50 values were lower than 5 μm. In particular, compounds 1a, 1c, 1d, and 1e bearing 3-bromophenyl groups were revealed as the most active antitumor drug candidates and had the average IC50 values of 1.

Rhodamine-based "turn-on" fluorescent probe with high selectivity for Fe(2+) imaging in living cells.

A rhodamine-based "turn-on" fluorescent probe 1 was synthesized with high yield. The recognizing behavior displays high selectivity of 1 toward Fe(2+) with a 2:1 complex, and 1 exhibits a stable response for Fe(2+) over a concentration range from 2 μM to 24 μM. Most importantly, probe is hardly interfered by other transition metal ions.

catena-Poly[[bis-(acetato-κO)aqua-copper(II)]-μ-5-(pyridin-3-yl)pyrimidine-κN:N].

In the title compound, [Cu(CH(3)CO(2))(2)(C(9)H(7)N(3))(H(2)O)](n), the Cu(II) ion is penta-coordinated in a square-pyramidal geometry. The N atoms of the two chelating symmetry-related 5-(pyridin-3-yl)pyrimidine ligands and the O atoms of the two monodentate acetate anions are nearly coplanar, with a mean deviation from the least-squares plane of 0.157 (2) Å and the Cu(II) ion is displaced by 0.

1-Benzyl-3,5-bis-(4-methyl-benzyl-idene)-4-oxopiperidin-1-ium chloride acetic acid monosolvate.

In the title solvated mol-ecular salt, C(28)H(28)NO(+)·Cl(-)·C(2)H(4)O(2), the central piperidinium ring of the cation adopts an envelope conformation with the N atom displaced by 0.798 (2) Å from the mean plane of the five C atoms. In the crystal, the components are linked by N-H⋯Cl and O-H⋯Cl hydrogen bonds into trimeric assemblies.