Pancreatic cancer is the fourth leading cause of related deaths in United States. The prognosis remains dismal with little advance treatment. Metformin a drug widely used for treatment type II diabetes. Recent epidemiologic data revealed that oral administration metformin associated reduced risk pancreatic cancer, suggesting its potential as novel this disease. Many studies have demonstrated vitro anticancer action metformin, but typically concentrations were much higher than vivo plasma and...

Cobaltacycle synthesis via C-H activation has been achieved for the first time, providing key mechanistic insight into cobalt catalytic chemistry. N-Chloroamides are used as a directing synthon cobalt-catalyzed room-temperature and construction of heterocycles. Alkynes coupling partners allow convenient access to isoquinolones, class synthetically pharmaceutically important compounds. The broad substrate scope enables diverse range substitution patterns be incorporated heterocyclic scaffold.

We report herein the development of a Co(III)-catalyzed enaminone-directed C–H amidation method for synthetic access to quinolones, an important heterocyclic scaffold diverse pharmaceutically active structures. The coupling with dioxazolones and subsequent deacylation installed amide group allow consecutive C–N generation quinolones wide-ranging compatible substituent patterns.

Abstract The prognosis of pancreatic cancer remains dismal, with little advance in chemotherapy because its high frequency chemoresistance. Metformin is widely used to treat type II diabetes and was shown recently inhibit stem cell proliferation. In the present study, we investigated role metformin chemoresistance cells gemcitabine possible cellular molecular mechanisms. increases sensitivity gemcitabine. mechanism involves, at least part, inhibition CD133 + proliferation suppression P70S6K...

At present, GPX4's role in the occurrence and development of diffuse large B lymphoma (DLBCL) is rarely reported. This study's purpose to explore significance diagnosis, treatment, pathological mechanisms DLBCL. The TIMER 2.0, GEPIA, GEO databases were used analyze expression levels DLBCL tissue, peripheral blood, single cells, evaluate its potential performance as a therapeutic diagnostic marker. Cell experiments validate cells. And revealed mechanism action from three aspects: immunity,...

Pancreatic cancer is one of the most lethal malignancies with poor prognosis. Previously, we found that a subpopulation stem cells (CSCs) in Panc-1 pancreatic cell line could propagate to form spheres. Here characterized malignant phenotypes CD44+/CD24+ cells, which were enriched under sphere forming conditions as analyzed by flow cytometry. These demonstrated increased resistance gemcitabine and migration ability. Moreover, these exhibited epithelial mesenchymal transition decreased level...

Valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, is reported to exert anti-tumor effects by upregulating the expression of natural killer group 2D (NKG2D) ligands on tumor cells; however, mechanisms vary in different types, and effect mechanism action VPA pancreatic cancer cells are unknown. The present study evaluated susceptibility NK cell-mediated lysis vitro vivo. Then we investigated which depend on. lactate dehydrogenase assay (LDH) xenograft experiment demonstrated that...

An efficient cobalt-catalyzed ring-opening reaction of bench-stable 1,2-oxazetidines with heteroarenes was unprecedentedly developed. The sustainable Cp*Co(III) catalyst enables a distinctive merger C–H activation concomitant N–O and C–C cleavages 1,2-oxazetidine, leading to site-selective aminomethylation hydroxymethylation heteroaromatic compounds containing broad range functional groups. Preliminary control experiments unravel some essential mechanistic features this one-pot transformation.

Multiphoton excitation allows one to access high energy excited states and perform valuable tasks in biological systems using tissue penetrating near-infrared (NIR) light. Here, we describe new photoactive manganese tricarbonyl complexes incorporating the ligand 4′-p-N,N-bis(2-hydroxyethyl)amino-benzyl-2,2′:6′,2″-terpyridine (TPYOH), which can serve as an antenna for two photon NIR excitation. Solutions of Mn(CO)3(TPYOH)X (X = Br– or CF3SO3–) are very toward CO release under visible light...

A C–H activation-based strategy has been developed for the synthesis of N-amino azaheterocycles. Rh(III)-catalyzed coupling N-Boc hydrazones/N-Boc hydrazines with diazodiesters/diazoketoesters provides convenient access to synthetically and medicinally important compounds, isoquinolin-3-ones indoles, by harnessing N-tert-butyloxycarbonyl (N-Boc) cleavage as an adaptable reactivity pattern in distinct synthetic scenarios.

Ruthenium-catalyzed heteroannulation between enamides and isocyanates has been realized as a complementary approach to conventional strategies for the synthesis of pyrimidin-4-ones. High step- atom-economy was achieved rapid construction such privileged scaffolds, which are found in multitude pharmaceutical compounds. The generality practicability this transformation were reflected by broad scope substrates with diverse functional groups, large-scale synthesis, late-stage diversification.

A trinuclear 3N-chelated monofunctional platinum complex, [Pt3(HPTAB)Cl3](ClO4)3 (HPTAB = N,N,N',N',N'',N''-hexakis(2-pyridylmethyl)-1,3,5-tris(aminomethyl)benzene), has been structurally characterized, which binds to DNA and demonstrates much higher potency against the murine leukemia cell line (P-388) human nonsmall-cell lung cancer (A-549) than cisplatin.

A mitochondrion-targeting Mn^II-terpyridine complex (MTP) has been developed for providing a good spatial condition to generate ¹O₂, which further promoted the two-photon photodynamic therapy (PDT) effect.

As the standard therapy for pancreatic cancer, gemcitabine shows limited efficacy in cancer patients because of chemoresistance. Aberrant expression Bmi1 has been reported to activate multiple growth-regulatory pathways and confer anti-apoptotic abilities many cells. However, role response cells towards resistance remains elusive. In this study, we found that certain dose treatment induced Knockdown enhanced ROS production promoted cytotoxic effect gemcitabine. The increased oxidative stress...

The terpyridine and its Zn(<sc>ii</sc>) complex process large conjugation system suitable electron donors, so that they display strong two-photon excited fluorescence.

Here we have designed and synthesized a novel analogous cis-platinum complex (TDPt) with strong two-photon absorption properties higher stability upon laser irradiation. Interestingly, cytotoxicity against three types of cancer cells compared to that commercial was observed. The initial confocal micrographs showed lysosomes may be the biological targets such TDPt, except conventional presumed DNA. This hypothesis further confirmed by microscopy transmission electron micrograph. These results...

Since the discovery of copper induces cell death(cuprotosis) in 2022, it has been one biggest research hotspots. cuprotosis related genes (CRGs) demonstrated to be a potential therapeutic target for cancer, however, molecular mechanism CRGs coronavirus disease 2019 (COVID-19) infected DLBCL patients not reported yet. Therefore, our objective is first elucidate and role COVID-19. Secondly, we conducted univariate multivariate analysis machine learning screen with common expression differences...

Neratinib, a typical small-molecule, pan-human tyrosine kinase inhibitor (TKI), has been licensed for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, underlying pharmacological mechanism is still unknown. In current study, we report novel function Neratinib by showing that its stimulates senescence mammary cancer AU565 cells. Our results demonstrate induces mitochondrial injury increasing reactive oxygen species (ROS) and reducing...