Photocatalytic [4 + 1] Cycloaddition Access to Multisubstituted 2-Imino-2,5-dihydrofurans.

Isocyanide radical cyclization, typically restricted to aryl isocyanides, is hampered by complex radical precursors. We've developed a strategy that overcomes this constraint by integrating [4 + 1] cyclization with a multifunctional system, which extends to alkyl and biomolecule-derived isocyanides and achieves a rare 1,2,3,4-tetrasubstitution of -unsaturated carbonyls. Over 50 2-imino-2,5-dihydrofuran derivatives have been synthesized, allowing for molecular skeleton editing into valuable frameworks.

Anticancer effects and mechanisms of , and on human lung carcinoma and hepatoma cells.

Herbs are extensively utilized in Traditional Chinese Medicine (TCM) for lung and liver cancer treatment, but the mechanisms behind these herbs remain largely unknown. Here, high-throughput transcriptomic analysis technology was used to uncover molecular mechanisms of herbal treatment. Furthermore, we developed a compound recognition approach utilizing the LINCS L1000 database to identify potential treatment targets.

Mechanism of Rabdosia rubescens extract against gastric cancer microenvironment by SIRT1/NF-κB/p53 pathway and promoting tumor-associated macrophage polarization.

Ethnopharmacological Relevance: The traditional action of Rabdosia rubescens (Hemsl.) H. Hara is heat-clearing and detoxifying, relieve sore throat, dissipate binds and disperse swelling.

Rhamnocitrin induces apoptosis of human nasopharyngeal carcinoma by inhibiting IGF-1R signaling pathway .

This study explored rhamnocitrin's apoptotic effects on human nasopharyngeal carcinoma cell lines (CNE-2/C666-1) and underlying mechanisms. Following treatment with varying concentrations, cell proliferation, apoptosis, and protein expression were analyzed using MTT assay, Hoechst/Annexin V-FITC/PI staining, and western blot. Results showed rhamnocitrin inhibited cell proliferation, induced apoptosis, downregulated IGF-1R, Erk1/2, and Akt phosphorylation, and activated caspase 3, caspase 8, caspase 9, and Bax while inhibiting survivin, Bcl-2, and Mcl-1.

Rutaecarpine derivatives synthesized skeletal reorganization alleviate inflammation-associated oxidative damage by inhibiting the MAPK/NF-κB signaling pathway.

In recent years, skeleton reorganization based on bioactive natural products has emerged as a novel alternative strategy to the classical approach, mainly focusing on the peripheral modification of the inherent natural skeleton. Such reorganizations not only afford structurally unique molecules but also provide unanticipated bioactivities compared with the unaltered natural precursors. Herein, by rebuilding the inherent rigid skeleton of cardioprotective rutaecarpine (RUT), thirty-three structural derivatives were designed and synthesized, with 5Ci being the most representative example, which exhibited superior protective effects against inflammation-induced ROS accumulation and cellular damage compared with the clinically used anti-inflammation drug indomethacin.

Screening -Derived Vesicles Harvested at Different Periods as Carriers for the Treatment of Colitis-Associated Cancer.

Plant-derived extracellular vesicles are of great significance in practical applications due to their availability, low immunogenicity, and effective carrier performance. -derived vesicles (IRDVs) not only have the capability for drug-carrying targeted therapy but also exhibit certain anti-inflammatory and antitumor effects as part of traditional Chinese medicine. The harvest time is closely related to the quality of its medicinal ingredients; however, whether there are differences in the IRDVs harvested at different times has yet to be explored.

Design, Synthesis and Bioactive Evaluation of Topo I/ Dual Inhibitors to Inhibit Oral Cancer via Regulating the PI3K/AKT/NF-κB Signaling Pathway.

The significantly rising incidence of oral cancer worldwide urgently requires the identification of novel, effective molecular targets to inhibit the progression of malignancy. DNA topoisomerase I (Topo I) is a well-established target for cancer treatment, and many studies have shown that different cancer cell genes could be targeted more selectively with one type of Topo I inhibitor. In this report, a new scaffold pyridothieno[3,2-]isoquinoline 11,11-dioxide was designed via the combination of the key fragment or bioisoster of Topo I inhibitor azaindenoisoquinolines and G-quadruplex binder quindoline.

Identification of O-arylated huperzinines as novel cholinergic anti-inflammatory pathway agonists against gout arthritis.

Lycodine alkaloids are important natural products with diverse biological effects. In this manuscript, we set out the first structural optimization of the 2-pyridone moiety of Lycodine alkaloid via selective O-arylation under metal-free conditions and obtained a series of potent bioactive molecules against monosodium urate (MSU)-induced IL-1β production. Further investigations demonstrated that these natural product derivatives could activate the neuro-immunomodulatory cholinergic anti-inflammatory pathway (CAP) to block the initial phase of NLRP3 inflammasome activation.

Synthesis of Indole-Fused Pyrazino[1,2-a]quinazolinones by Copper(I)-Catalyzed Selective Hydroamination-Cyclization of Alkynyl-tethered Quinazolinones.

We described a copper(I)-catalyzed atom economic and selective hydroamination-cyclization of alkynyl-tethered quinazolinones to prepare a variety of indole-fused pyrazino[1,2-a]quinazolinones in good to excellent yields ranging from 39 %-99 % under mild reaction conditions. Control experiments revealed that coordination-directed method of quinazolinone moiety with copper(I) was important for the selective hydroamination-cyclization of alkynes at the N1-atom instead of N3-atom of quinazolinone. The reaction could be easily performed at gram scales and some prepared indole-fused pyrazino[1,2-a]quinazolinones with donating groups on the indole moiety showed a distinct fluorescence emission wavelength with blue shift under the acid conditions.

Effect of traditional Chinese medicine on metabolism disturbance in ischemic heart diseases.

Ethnopharmacological Relevance: Ischemic heart diseases (IHD), characterized by metabolic dysregulation, contributes majorly to the global morbidity and mortality. Glucose, lipid and amino acid metabolism are critical energy production for cardiomyocytes, and disturbances of these metabolism lead to the cardiac injury. Traditional Chinese medicine (TCM), widely used for treating IHD, have been demonstrated to effectively and safely regulate the cardiac metabolism reprogramming.

Synthesis of 4-(trichloromethyl)pyrido[2',1':3,4]pyrazino[2,1-]quinazolinones through a cyclized dearomatization and trichloromethylation cascade strategy.

A variety of 4-(trichloromethyl)pyrido[2',1':3,4]pyrazino[2,1-]quinazolinones were prepared in moderate to good yields with high regioselectivity through intramolecular 6- cyclization and trichloromethylation of 3-alkynyl-2-pyridinyl-tethered quinazolinones in chloroform. Mechanistic studies revealed that chloroform might serve as a trichloromethyl anion precursor. Furthermore, the reaction could be easily performed on gram scales and an estrone-derived 4-(trichloromethyl)pyrido[2',1':3,4]pyrazino[2,1-]quinazolinone was prepared over five steps.

Copper(I)-Catalyzed Dearomatization of Benzofurans with 2-(Chloromethyl)anilines through Radical Addition and Cyclization Cascade.

Herein, we described a copper(I)-catalyzed dearomatization of benzofurans with 2-(chloromethyl)anilines to prepare various tetrahydrobenzofuro[3,2-]quinolines and 2-(quinolin-2-yl)phenols in good to excellent yields through radical addition and an intramolecular cyclization process. Mechanistic studies revealed that 2-(chloromethyl)anilines served as radical precursors. The present method features broad substrate scope, good functional group tolerance, quinoline scaffold diversity, and radical addition dearomatization of benzofurans.

Design and synthesis of luotonin A-derived topoisomerase targeting scaffold with potent antitumor effect and low genotoxicity.

Conventional topoisomerase (Topo) inhibitors typically usually exert their cytotoxicity by damaging the DNAs, which exhibit high toxicity and tend to result in secondary carcinogenesis risk. Molecules that have potent topoisomerase inhibitory activity but involve less DNA damage provide more desirable scaffolds for developing novel chemotherapeutic agents. In this work, we broke the rigid pentacyclic system of luotonin A and synthesized thirty-three compounds as potential Topo inhibitors based on the devised molecular motif.

Radical-Based -Selective Annulations of '-Cyclic Azomethine Imines with -Sulfonyl Cyclopropylamines.

Azomethine imines, broadly known as 1,3-dipoles, efficiently produce synthetically and biologically significant dinitrogen-fused heterocycles via predominantly concerted or ionic pathways. Herein, we describe a radical-based annulation of azomethine imines utilizing visible-light photoredox catalysis for the first time. This strategy enables the synthesis of dinitrogen-fused saturated six-membered cyclic products that have traditionally been difficult to access.

Advancements in the Biotransformation and Biosynthesis of the Primary Active Flavonoids Derived from .

is a classical Chinese herbal medicine, which has been used extensively to treat various diseases, such as sexual dysfunction, osteoporosis, cancer, rheumatoid arthritis, and brain diseases. Flavonoids, such as icariin, baohuoside I, icaritin, and epimedin C, are the main active ingredients with diverse pharmacological activities. Currently, most flavonoids are extracted from plants, but this method cannot meet the increasing market demand.

The Merger of Halogen Atom Transfer (XAT) and Energy Transfer Catalysis (EnT) for the Modular 1,2-Iminylalkylation of Diazenes.

The 1,2-iminylalkylation of diazenes using alkyl iodides in combination with an -benzoyl oxime is reported. In this transformation, -benzoyl oxime acted as a radical precursor and XAT mediator. In addition to common alkyl iodides, other alkyl iodides such as iodomethane, iodomethane-, trifluoroiodomethane, ethyl difluoroiodoacetate, and iodoalkanes containing unprotected hydroxyl and amide groups can also serve as C-radical precursors in the 1,2-iminylalkylation with electrophilic diazenes as radical acceptors.

Design and synthesis of pseudo-rutaecarpines as potent anti-inflammatory agents via regulating MAPK/NF-κB pathways to relieve inflammation-induced acute liver injury in mice.

Pseudo-natural products (PNPs) design strategy provides a great valuable entrance to effectively identify of novel bioactive scaffolds. In this report, novel pseudo-rutaecarpines were designed via the combination of several privileged structure units and 46 target compounds were synthesized. Most of them display moderate to potent inhibitory effect on LPS-induced NO production and low cytotoxicity in RAW264.

Photoinduced Remote C(sp)-H Imination Enabled by Vinyl Radical-Mediated 1,5-Hydrogen Atom Transfer.

A vinyl radical-mediated 1,5-hydrogen atom transfer strategy for remote C(sp)-H imination under visible-light-induced photochemical metal-free conditions afforded diverse γ-imino alkenes with excellent stereoselectivity. Oxime ester-based bifunctional reagents provided not only nucleophilic alkyl radicals for radical addition reactions with electron-deficient alkynes but also long-lived steady-state imine radicals for trapping alkyl radicals following the intramolecular 1,5-hydrogen migration of unstable olefin radicals.

Research advances in probiotic fermentation of Chinese herbal medicines.

Chinese herbal medicines (CHM) have been used to cure diseases for thousands of years. However, the bioactive ingredients of CHM are complex, and some CHM natural products cannot be directly absorbed by humans and animals. Moreover, the contents of most bioactive ingredients in CHM are low, and some natural products are toxic to humans and animals.

Synthesis of spiroindolenine-3,3'-pyrrolo[2,1-]quinazolinones through gold(I)-catalyzed dearomative cyclization of -alkynyl quinazolinone-tethered indoles.

A variety of functionalized spiroindolenine-3,3'-pyrrolo[2,1-]quinazolinones were prepared in good to excellent yields through a gold(I)-catalyzed dearomative cyclization of -alkynyl quinazolinone-tethered C2-substituted indoles. This reaction features a broad substrate scope, good functional group tolerance, and easy gram-scale preparation and transformations. Furthermore, biological activity studies showed that most of the obtained spiroindolenine-3,3'-pyrrolo[2,1-]quinazolinone scaffolds showed potential as good anti-inflammatory agents.

Luteolin combined with low-dose paclitaxel synergistically inhibits epithelial-mesenchymal transition and induces cell apoptosis on esophageal carcinoma in vitro and in vivo.

Although paclitaxel is a promising frontline chemotherapy agent for various malignancies, the clinical applications have been restricted by side effects, drug resistance, and cancer metastasis. The combination of paclitaxel and other agents could be the promising strategies against malignant tumor, which enhances the antitumor effect through synergistic effects, reduces required drug concentrations, and also suppresses tumorigenesis in multiple ways. In this study, we found that luteolin, a natural flavonoid compound, combined with low-dose paclitaxel synergistically regulated the proliferation, migration, epithelial-mesenchymal transition (EMT), and apoptosis of esophageal cancer cells in vitro, as well as synergistically inhibited tumor growth without obvious toxicity in vivo.

3-Arylamino-quinoxaline-2-carboxamides inhibit the PI3K/Akt/mTOR signaling pathways to activate P53 and induce apoptosis.

Thirty-eight new 3-arylaminoquinoxaline-2-carboxamide derivatives were in silico designed, synthesized and their cytotoxicity against five human cancer cell lines and one normal cells WI-38 were evaluated. Molecular mechanism studies indicated that N-(3-Aminopropyl)-3-(4-chlorophenyl) amino-quinoxaline-2-carboxamide (6be), the compound with the most potent anti-proliferation can inhibit the PI3K-Akt-mTOR pathway via down regulating the levels of PI3K, Akt, p-Akt, p-mTOR and simultaneously inhibit the phosphorylation of Thr308 and Ser473 residues in Akt kinase to servers as a dual inhibitor. Further investigation revealed that 6be activate the P53 signal pathway, modulated the downstream target gene of Akt kinase such p21, p27, Bax and Bcl-2, caused the fluctuation of intracellular ROS, Ca and mitochondrial membrane potential to induce cell cycle arrest and apoptosis in MGC-803 cells.

EMT and Cancer Cell Stemness Associated With Chemotherapeutic Resistance in Esophageal Cancer.

Drug resistance often occurs after chemotherapy in esophageal cancer patients, leading to cancer metastasis and recurrence. However, the relationship among cancer cell migration, recurrence and drug resistance in esophageal cancer drug-resistant cells has not been clearly explained. In this study, we constructed paclitaxel (PTX)-resistant esophageal cancer cells to explore the causes of drug resistance and poor prognosis after chemotherapy in esophageal cancer.