Dearomative Cyclization/Spirocyclization via Electrochemical Reductive Hydroarylation of Nonactivated Arenes.

An electrochemical cyclization/spirocyclization hydroarylation via reductive dearomatization of a series of nonactivated arenes including -substituted indoles, indole-3-carboxamide derivatives, and iodo-substituted benzamides is described. This protocol boasts high atom efficiency, broad substrate applicability, and excellent selectivity. Utilizing a simple undivided cell, various nonactivated arenes undergo cyclization/spirocyclization through the intramolecular addition of aryl radicals to an aromatic ring, yielding 50 indolines, spirocyclizative hydroarylation products, and phenanthridinones.

Discovery of novel 1,8-naphthalimide piperazinamide based benzenesulfonamides derivatives as potent carbonic anhydrase IX inhibitors and ferroptosis inducers for the treatment of triple-negative breast cancer.

A novel series of 1,8-naphthalimide piperazinamide based benzenesulfonamides derivatives were designed and synthesized as carbonic anhydrase IX (CA IX) inhibitors and ferroptosis inducers for the treatment of triple-negative breast cancer (TNBC). The representative compound 9o exhibited more potent inhibitory activity and selective against CA IX over off-target CA II, compared with positive control SLC-0111. Molecular docking study was also performed to gain insights into the binding interactions of 9o in the binding pocket of CAIX.

The potential of carbonic anhydrase enzymes as a novel target for anti-cancer treatment.

Carbonic anhydrase (CA) is a zinc-dependent metal enzyme that maintains the pH and carbon dioxide (CO) homeostasis in cells by catalyzing the reversible hydration and dehydration of CO and bicarbonate (HCO). In mammals, there are 16 isozymes of CA existed, namely CAI to CAXIV, but only 15 isozymes are found in humans except CAXV. Human CAs have highly conserved catalytic domains, all of which are distributed in different tissues and play important physiological roles.

Design, docking optimization, and evaluation of biotin-PEG4-1,8-naphthalimide as a potent and safe antitumor agent with dual targeting of ferroptosis and DNA.

A set of biotin-polyethylene glycol (PEG)-naphthalimide derivatives 4a-4h with dual targeting of ferroptosis and DNA were designed and optimized using docking simulation as antitumor agents. Docking simulation optimization results indicated that biotin-PEG4-piperazine-1,8-naphthalimide 4d should be the best candidate among these designed compounds 4a-4h, and therefore, we synthesized and evaluated it as a novel antitumor agent. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and MGC-803 and U251 xenograft models identified 4d as a good candidate antitumor agent with potent efficacy and safety profiles, compared with amonafide and temozolomide.

An Effective and Promising Strategy for Plant Protection: Synthesis of -Carvone-Based Thiazolinone-Hydrazone/Nanochitosan Complexes with Antifungal Activity and Sustained Releasing Performance.

The development of novel natural product-derived nano-pesticide systems with loading capacity and sustained releasing performance of bioactive compounds is considered an effective and promising plant protection strategy. In this work, 25 -carvone-based thiazolinone-hydrazone compounds ~ were synthesized by the multi-step modification of -carvone and structurally confirmed. Compound was found to show favorable and broad-spectrum antifungal activity through the in vitro antifungal activity evaluation of compounds ~ against eight phytopathogenic fungi.

Electrochemical Oxidative Difunctionalization of Diazo Compounds with Diselenides and Nucleophiles.

An electrochemical oxidative difunctionalization of diazo compounds with diselenides and nucleophiles has been developed. This innovative approach yields a diverse array of selenium-containing pyrazole esters and alkoxy esters, overcoming the limitations of traditional synthesis methods. Remarkably, various nucleophiles, including acids, alcohols, and pyrazoles, can be seamlessly incorporated.

Design, synthesis, and antiproliferative evaluation of novel dehydroabietic acid-1,2,3-triazole-oxazolidinone hybrids.

A series of novel dehydroabietic acid derivatives containing both 1,2,3-triazole and oxazolidinone 4a-4t have been synthesized and their antiproliferative activity against HeLa, HepG2, MGC-803 and T-24 cell lines evaluated. Most of them displayed cell proliferation inhibition on four tested human malignant tumour cell lines to some degree. Among them, compound 4p exhibited promising cytotoxicity with IC values ranging from 3.

Discovery of 4-(N-dithiobenzyl piperazine)-1,8-naphthalimide as a potent multi-target antitumor agent with good efficacy, limited toxicity, and low resistance.

A series of 4-(N-dithiobenzyl piperazine)-1,8-naphthalimide derivatives 4-6 were designed, synthesized, and evaluated as novel multi-target antitumor agents. 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) results showed that compounds 5j, 5k, and 6j exhibited superior in vitro antiproliferative activity in MGC-803, HepG-2, SKOV-3, and T24 cancer cell lines and the cisplatin-resistant cell line A549/DDP. HepG-2, SKOV-3, and T24 xenograft assay results revealed that compounds 5j, 5k, and 6j exhibited good antitumor effects compared with amonafide.

Synthesis and Biological Evaluation of Novel 2-Amino-1,4-Naphthoquinone Amide-Oxime Derivatives as Potent IDO1/STAT3 Dual Inhibitors with Prospective Antitumor Effects.

Indoleamine-2,3-dioxygenase 1 (IDO1) and signal transducer and activator of transcription 3 (STAT3) have emerged as significant targets in the tumor microenvironment for cancer therapy. In this study, we synthesized three novel 2-amino-1,4-naphthoquinone amide-oxime derivatives and identified them as dual inhibitors of IDO1 and STAT3. The representative compound demonstrated effective binding to IDO1 and exhibited good inhibitory activity (hIDO1 IC = 0.

Synthesis and anti-proliferative activity of dehydroabietinol derivatives bearing a triazole moiety.

In search of more efficacious antitumor agents, a series of novel dehydroabietinol derivatives containing a triazole moiety was synthesized, and evaluated for cytotoxicity against four human cancer cell lines. Many exhibited superior cytotoxic profiles compared to the parent molecule, dehydroabietic acid. In particular, compounds 5g, 5i and 5j exhibited promising cytotoxicity with IC values ranging from 4.

Discovery of novel sulfonamide chromone-oxime derivatives as potent indoleamine 2,3-dioxygenase 1 inhibitors.

A series of chromone-oxime derivatives containing piperazine sulfonamide moieties were designed, synthesized and evaluated for their inhibitory activities against IDO1. These compounds displayed moderate to good inhibitory activity against IDO1 with IC values in low micromolar range. Among them, compound 10m bound effectively to IDO1 with good inhibitory activities (hIDO1 IC = 0.

Causal Associations of PM2.5 and GDM: A Two-Sample Mendelian Randomization Study.

Epidemiological studies have linked particulate matter (PM2.5) to gestational diabetes mellitus (GDM). However, the causality of this association has not been established; Mendelian randomization was carried out using summary data from genome-wide association studies (GWAS).

SERS- and absorbance-based catalytic assay for determination of isocarbophos using aptamer-modified FeMOF nanozyme and in situ generated silver nanoparticles.

A new Fe metal-organic framework-loaded liquid crystal 4-octoxybenzoic acid (FeMOF@OCTB) nanosol was synthesized using 1,3,5-phthalic acid, ferrous sulfate, and OCTB as precursors. The FeMOF@OCTB exhibits good stability and strong catalytic effect for the polyethylene glycol 400-Ag (I) indicator reaction, which was evaluated rapidly by the slope procedure. The generated silver nanoparticles have a strong surface-enhanced Raman scattering (SERS) effect and a surface plasmon resonance absorption (Abs) peak at 420 nm.

Ursolic acid-piperazine-dithiocarbamate ruthenium(II) polypyridyl complexes induced necroptosis in MGC-803 cells.

Three ursolic acid-piperazine-dithiocarbamate ruthenium(II) polypyridyl complexes Ru1-Ru3 were designed and synthesized for evaluating antitumor activity. All the complexes exhibited high in vitro cytotoxicity against MGC-803, T24, HepG2, CNE2, MDA-MB-231, MCF-7, A549, and A549/DDP cell lines. Ru1, Ru2, and Ru3 were 11, 8 and 10 times, respectively, more active than cisplatin against A549/DDP.

[The Tertiary Hospital's Medical Materials Supply in the Prevention of Public Health Emergencies].

Objective: To ensure the supply of prevention materials in the tertiary public hospitals in prefecturelevel cities, and to make the process of allocating prevention materials more scientific and reasonable.

Methods: Open the green passage, simplify the procurement process, carry out emergency procurement of related materials, ensure timely delivery of prevention materials, distribute them at different levels, and strengthen the warehouse management of prevention materials.

Results: The scheme of emergancy supplies was constantly improved, and the supply of prevention materials was completed with good quality.

Visible-Light-Induced Tandem Reaction of Allenes with Selenesulfonates Leading to ()-2,3-Disulfonylpropene Derivatives.

A visible-light-induced tandem reaction of allenes with selenesulfonates was developed, providing ()-2,3-disulfonylpropene derivatives in moderate to good yields. This reaction was featured with simple operation, good regioselectivity and stereoselectivity, and wide functional group tolerance. Photoinduced radical additions via energy transfer were proposed.

Design, Synthesis and Pharmacological Evaluation of Three Novel Dehydroabietyl Piperazine Dithiocarbamate Ruthenium (II) Polypyridyl Complexes as Potential Antitumor Agents: DNA Damage, Cell Cycle Arrest and Apoptosis Induction.

The use of cisplatin is severely limited by its toxic side-effects, which has spurred chemists to employ different strategies in the development of new metal-based anticancer agents. Here, three novel dehydroabietyl piperazine dithiocarbamate ruthenium (II) polypyridyl complexes (-) were synthesized as antitumor agents. Compounds and exhibited better in vitro antiproliferative activity against seven tumor cell lines than cisplatin, they displayed no evident resistance in the cisplatin-resistant cell line A549/DPP.

Synthesis and biological evaluation of dehydroabietic acid-pyrimidine hybrids as antitumor agents.

A series of novel dehydroabietic acid derivatives containing pyrimidine moieties were designed and synthesized to explore more efficacious and less toxic antitumor agents according to the principle of combination and hybridization. The cytotoxicity against human liver cancer (HepG2) cells, human breast cancer (MCF-7) cells, human colon cancer (HCT-116) cells, human lung cancer (A549) cells, and human normal liver cells (LO2) was estimated by MTT assay . Cytotoxic activity screening revealed that most of the compounds showed moderate to high levels of cytotoxicity against these four cancer cell lines and that some displayed more potent inhibitory activities compared with 5-FU.

Visible-Light-Promoted Selenylative Spirocyclization of Indolyl-ynones toward the Formation of 3-Selenospiroindolenine Anticancer Agents.

A metal-free and efficient visible-light-induced spirocyclization of indolyl-ynones with diselenides at room temperature under air atmosphere to prepare 3-selenospiroindolenines in moderate to good yields has been developed. The resulting products were tested for in vitro anticancer activity by MTT assay, and compounds 3 c and 3 e showed potent cancer cell-growth inhibition activities.

Design, synthesis and biological evaluation of 3-nitro-1,8-naphthalimides as potential antitumor agents.

A series of 3-nitro-naphthalimides 1(1a-1h) were designed and synthesized as antitumor agents. MTT assay results showed that all these compounds exhibited obvious antiproliferative activity against SKOV3, HepG2, A549, T-24 and SMMC-7721 cancer cell lines, while compound 1a displayed the best antiproliferative activity against HepG2 and T-24 cell lines in comparison with mitonafide, with IC of 9.2 ± 1.

Synthesis and Antiproliferative Evaluation of Novel Hybrids of Dehydroabietic Acid Bearing 1,2,3-Triazole Moiety.

To discover novel potent cytotoxic diterpenoids, a series of hybrids of dehydroabietic acid containing 1,2,3-triazole moiety were designed and synthesized. The target compounds were characterized by means of FT-IR, H NMR, C NMR, ESI-MS and elemental analysis techniques. The in vitro cytotoxicity of these compounds was evaluated by standard MTT (methyl thiazolytetrazolium) assay against CNE-2 (nasopharynx), HepG2 (liver), HeLa (epithelial cervical), BEL-7402 (liver) human carcinoma cell lines and human normal liver cell (HL-7702).

Visible Light-Induced Difunctionalization of Alkynes: The Synthesis of Thiazoles and 1,1-Dibromo-1-en-3-ynes.

A visible light-induced cascade cyclization of thioamides with alkynes was developed to synthesize 1,3-thiozoles. The sulfur radical generated from thioamide via the single-electron transfer (SET) pathway was promoted by photocatalysis as a key intermediate in this reaction. When bromoalkynes were used as the substrate, the self-coupling products 1,1-dibromo-1-en-3-ynes were obtained in moderate yields, and an energy transfer pathway for this transformation promoted by visible-light photocatalysis was proposed.

Synthesis and Biological Evaluation of Novel Dehydroabietic Acid-Oxazolidinone Hybrids for Antitumor Properties.

Novel representatives of the important group of biologically-active, dehydroabietic acid-bearing oxazolidinone moiety were synthesized to explore more efficacious and less toxic antitumor agents. Structures of all the newly target molecules were confirmed by IR, ¹H-NMR, C-NMR, and HR-MS. The inhibitory activities of these compounds against different human cancer cell lines (MGC-803, CNE-2, SK-OV-3, NCI-H460) and human normal liver cell line LO2 were evaluated and compared with the commercial anticancer drug cisplatin, using standard MTT (methyl thiazolytetrazolium) assay in vitro.

Design, synthesis and pharmacological evaluation of novel 2-chloro-3-(1-benzo[]imidazol-2-yl)quinoline derivatives as antitumor agents: and antitumor activity, cell cycle arrest and apoptotic response.

A series of novel 2-chloro-3-(1-benzo[]imidazol-2-yl)quinoline derivatives (3a-3d) were designed and synthesized as antitumor agents. antitumor assay results showed that some compounds exhibited moderate to high inhibitory activities against HepG2, SK-OV-3, NCI-H460 and BEL-7404 tumor cell lines, and most compounds exhibited much lower cytotoxicities against HL-7702 normal cell line compared to 5-FU and cisplatin. antitumor assay results showed that the representative compound 3a exhibited effective inhibition on tumor growth in the HepG2 xenograft mouse model.