The novel selective TLR7 agonist GY101 suppresses colon cancer growth by stimulating immune cells.

Toll-like receptor (TLR) 7, a transmembrane signal transduction receptor expressed on the surface of endosomes, has become an attractive target for antiviral and cancer immunotherapies. TLR7 can induce signal transduction by recognizing single-stranded RNA or its analogs, leading to the release of cytokines such as IL-6, IL-12, TNF-α and type-I IFN. Activation of TLR7 helps to enhance immunogenicity and immune memory by stimulating immune cells.

Azvudine is a thymus-homing anti-SARS-CoV-2 drug effective in treating COVID-19 patients.

Azvudine (FNC) is a nucleoside analog that inhibits HIV-1 RNA-dependent RNA polymerase (RdRp). Recently, we discovered FNC an agent against SARS-CoV-2, and have taken it into Phase III trial for COVID-19 patients. FNC monophosphate analog inhibited SARS-CoV-2 and HCoV-OC43 coronavirus with an EC between 1.

Dinuclear Zinc-Catalyzed Asymmetric Tandem Reaction of α-Hydroxy-1-indanone: Access to Spiro[1-indanone-5,2'-γ-butyrolactones].

A highly efficient method for the enantioselective build of spiro[1-indanone-5,2'-γ-butyrolactones] has been developed through the tandem Michael/transesterification reaction of α-hydroxy-1-indanone and -unsaturated esters. A broad range of spiro(1-indanone-butyrolacones) with contiguous stereocenters have been synthesized with excellent stereoselectivities (up to >20:1 dr, up to >99% ee) under the catalysis of dinuclear zinc complex. Moreover, the reaction can be run on a gram scale without affecting its stereoselectivities.

Synthesis of Chiral Bispirotetrahydrofuran Oxindoles by Cooperative Bimetallic-Catalyzed Asymmetric Cascade Reaction.

A new, efficient route for the enantioselective construction of bispirotetrahydrofuran oxindoles is described via the cooperative dinuclear zinc-AzePhenol catalyst. Under mild conditions, a broad range of bispirotetrahydrofuran oxindoles have been synthesized with excellent stereoselectivities through the cascade Michael/hemiketalization/Friedel-Crafts reaction of β,γ-unsaturated α-ketoamide and 2-hydroxy-1-indanone. The reaction can be performed on a gram scale with low catalyst loading (2 mol %) without impacting its efficiency.

Preclinical Pharmacokinetics, Tissue Distribution, and Plasma Protein Binding of Sodium (±)-5-Bromo-2-(α-Hydroxypentyl) Benzoate (BZP), an Innovative Potent Anti-ischemic Stroke Agent.

Sodium (±)-5-bromo-2-(α-hydroxypentyl) benzoate (BZP) is a potential cardiovascular drug and exerts potent neuroprotective effect against transient and long-term ischemic stroke in rats. BZP could convert into 3-butyl-6-bromo-1(3H)-isobenzofuranone (Br-NBP) in vitro and in vivo. However, the pharmacokinetic profiles of BZP and Br-NBP still have not been evaluated.

A New Strategy for Enantioselective Construction of Multisubstituted Five-Membered Oxygen Heterocycles via a Domino Michael/Hemiketalization Reaction.

A new highly enantioselective domino Michael/hemiketalization reaction of α-hydroxyacetophenone with β,γ-unsaturated α-keto esters for the synthesis of 2,2,4,5-tetrasubstituted chiral tetrahydrofurans is reported. With 2 mol % intramolecular dinuclear zinc-AzePhenol complex prepared in situ from the reaction of multidentate semi-azacrown ether ligand with ZnEt2 , the corresponding anti-multisubstituted tetrahydrofuran products were obtained in up to 90 % yields, and 98 % enantiomeric excess (ee) at 0 °C for 45 min. Moreover, the products were easily converted to 2,3,5-trisubstituted 2,3-dihydrofurans without any loss in optical activity.

Biodegradable PLGA nanoparticles loaded with hydrophobic drugs: confocal Raman microspectroscopic characterization.

Poly(lactic-co-glycolic acid) (PLGA) nanoparticles with bicyclol (5%) and 3-n-butyl-6-bromophthalid (Br-NBP) (3%) were prepared by an emulsification-solvent evaporation technique. The PLGA nanoparticles were, for the first time, successfully characterized by a laser trapping/confocal Raman spectroscopic technique using only individual PLGA nanoparticles. This technique allowed us to selectively obtain Raman spectra of optically trapped PLGA nanoparticles (∼10 nanoparticles) in solution.

Enantioselective Friedel-Crafts alkylation of pyrrole with chalcones catalyzed by a dinuclear zinc catalyst.

A highly enantioselective Friedel-Crafts (F-C) alkylation of pyrrole with a wide range of simple nonchelating chalcone derivatives catalyzed by a chiral (Zn2EtL)n (L = (S,S)-1) complex has been developed. The catalyst (Zn2EtL)n complex was prepared in situ by reacting the chiral ligand (S,S)-1 with 2 equiv of diethylzinc. A series of β-pyrrole-substituted dihydrochalcones were usually formed mostly in excellent yields (up to 99%) and excellent enantioselectivity [up to 99% enantiomeric excess (ee)] by using 15 mol % catalyst loading under mild conditions.

FNC, a novel nucleoside analogue, blocks invasion of aggressive non-Hodgkin lymphoma cell lines via inhibition of the Wnt/β-catenin signaling pathway.

Chemotherapy is the primary therapy for malignant lymphoma (ML). However, the clinical outcome is still far from satisfactory. Consequently, an understanding of the mechanism of modulating cancer cell invasion, migration and metastasis is important for the development of more effective chemotherapeutic agents.

Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro.

Azvudine is a novel nucleoside reverse transcriptase inhibitor with antiviral activity on human immunodeficiency virus, hepatitis B virus and hepatitis C virus. Here we reported the in vitro activity of azvudine against HIV-1 and HIV-2 when used alone or in combination with other antiretroviral drugs and its drug resistance features. Azvudine exerted highly potent inhibition on HIV-1 (EC(50)s ranging from 0.

Highly enantioselective catalytic system for asymmetric copolymerization of carbon dioxide and cyclohexene oxide.

A new ligand can be easily prepared, and its intramolecular dinuclear zinc complexes act as a high performance catalyst for the asymmetric alternating copolymerization of cyclohexene oxide and CO2 under very mild conditions (1 atm CO2 , room temperature), affording completely alternating polycarbonates with up to 93.8 % enantiomeric excess (ee) and 98 % yield. A high Mn value of 28 600 and a relatively narrow polydispersity (Mw /Mn ratio) of 1.

Polygonumosides A-D, stilbene derivatives from processed roots of Polygonum multiflorum.

Four new stilbene derivatives, polygonumosides A-D (1-4), were isolated from the processed roots of Polygonum multiflorum. Their structures were elucidated by spectroscopic analysis, including 1D and 2D NMR and ECD. Polygonumosides A (1) and B (2), possessing an unprecedented tetracyclic skeleton, were assigned as 2S- and 2R-2-(4-hydroxyphenyl)-9,10,11-trihydroxy-2H-benzo[c]furo[2,3-f]chromen-7(3H)-one-4-O-β-d-glucopyranosides, respectively, while polygonumosides C (3) and D (4) were assigned as a pair of diastereomeric stilbene glucoside dimers.

[Effect of release of hydroxypropylmethyl cellulose on single and bilayer sustained-release matrix tablets].

Objective: To study the influence of HPMC as hydrophilic matrix materials and controlled-layer components on the drug release of sustained-release matrix tablets and bilayer tablets.

Methods: Diltiazem hydrochloride was chosen as the water-soluble model drug to prepare different kinds of matrix tablets and double layer tablets with different formulations, and evaluate how the levels and grades of HPMC affect the drug release in sustained-release tablets and bilayer tablets.

Results: HPMC with high viscosity and the amount of 20%-40% could delay the drug release to certain degree, but it was difficult to further slow down the drug release up to 24 h, especially for a water soluble drug.

Anti-hepatitis B virus activity of α-DDB-DU, a novel nucleoside analogue, in vitro and in vivo.

α-DDB-DU, 2'-deoxy-3'-(4,4'-dimethoxy-2'-methoxycarbonyl-5,6,5',6'-bis(methylenedioxy)-1,1'-biphenyl-2-carboxyl)uridine, is a novel nucleoside analogue accomplished by linking α-DDB (α-dimenthoxy dicarboxylate biphenyl) and DU (2'-deoxyuridine) via an ester bond. In the current study, the anti-HBV activity and hepatoprotective effect of this compound were investigated both in vitro and in vivo. In the human HBV-transfected liver cell line HepG2.

The discovery of SYP-10913 and SYP-11277: novel strobilurin acaricides.

Background: As previously reported, methyl (E)-2-[2-(2-phenylamino-6-trifluoromethylpyrimidin-4-yloxymethyl)phenyl]-3-methoxyacrylate has proven to be a new lead with highly acaricidal activity. Following on from this, in an effort to discover new strobilurin analogues with improved activity, a series of substituted pyrimidines were synthesised and bioassayed.

Results: All compounds were characterised by (1) H NMR, IR, MS and elemental analysis.

[Novel synthetic method and analgesic activity of tepoxalin].

Tepoxalin is a potent inhibitor of both the cyclooxygenase and lipoxygenase pathways of the arachidonic acid cascade, as well as a potent anti-inflammatory and control-pain (postoperation, arthritis et. al.) agent.

Protective effect of 3-butyl-6-bromo-1(3H)-isobenzofuranone on hydrogen peroxide-induced damage in PC12 cells.

Oxidative stress, an imbalance toward the prooxidant side of the prooxidant/antioxidant homeostasis, occurs in several brain neurodegenerative disorders. The protective effect of 3-butyl-6-bromo-1(3H)-isobenzofuranone (Br-NBP), a derivative compound of l-3-n-butylphthalide (NBP), on the hydrogen peroxide(H(2)O(2))- induced oxidative damage was investigated in PC12 cells. Following exposure of the cells to H(2)O(2), there was a significant reduction in cell survival,activities of glutathione peroxidase (GSH-px) and mitochondria membrane potential(MMP), in contrast, the increased levels in the leakage of lactate dehydrogenase (LDH), malondialdehyde (MDA) contents, nitric oxide (NO) productions, intracellular reactive oxygen species (ROS), intracellular Ca(2+) concentration ([Ca(2+)](i)), as well as cell apoptosis were observed.

Design, synthesis and acaricidal activity of novel strobilurin derivatives containing pyrimidine moieties.

Background: The intermediate derivatisation method based on bioisosteric replacement led to the discovery of the lead strobilurin compound 5a. To produce new strobilurin analogues with improved activity, a series of substituted pyrimidines were synthesised and bioassayed.

Results: The compounds were identified by (1)H NMR, IR, MS and elemental analysis.

[IR and Raman spectroscopic studies on the derivatives of butylphthalide].

dl-NBP is a potentially beneficial and promising drug for treatment of ischemic stroke with multiple actions that affect different pathophysiologic processes, such as improving microcirculation, decreasing brain infarct volume, regulating energy metabolism, and especially inhibiting platelet aggregation and reducing thrombus formation. However, NBP is limited to use in the clinic by other side effects, such as elevated aminotransferase, abnormal liver function and digestive response. Some derivates of NBP were synthesized with the halides (F, Cl and Br) on the 6-position, and their IR and Raman spectra were measured.

[FTIR study on the synthesis of poly(propylene fumarate) and its copolymer].

Poly(propylene fumarate) (PPF) is one kind of linear biodegradable polyester and the unsaturated double bonds along its main chain can be crosslinked with other olefinic monomers to form three-dimensional networks, and the networks can support tissues. In the present paper, firstly, the intermediate oligomer-bis (2-hydroxypropyl) fumarate (PFP) was synthesized, and then the unsaturated linear polyester PPF was synthesized with the oligomer PFP through melting condensation process. Additionally, on the base of the process, the oligomer bis(2-hydroxypropyl) sebacate (PSP) was synthesized by similar method and then a kind of new copolymer named poly(propylene fumarate-co-propylene sebacate) [P(PF-co-PS)] that comprised bis(2-hydroxypropyl) sebacate segments was synthesized with PFP and PSP by melting condensation.

Synthesis and biological activity of n-butylphthalide derivatives.

A series of n-butylphthalide derivatives were designed and synthesized. The in vitro activities of these compounds were evaluated by a resting tension of isolated rat thoracic aorta ring assay. Compounds 4g and 4i were found to be more active than n-butylphthalide.

[Study on the circular dichroism of (S)- and (R)- Wuweizisu C].

The circular dichroism (CD) is an excellent method for determining the absolute stereochemistry of organic compounds. The CD spectra of four biphenyl compounds were determined by using CD spectrometer, and two pairs of symmetrical CD spectra were obtained. The absolute configuration of biphenyl bond was confirmed by the Cotton effect according to the CD rule.

[Study on spectroscopy of 3-substituted phenyl-5-(3'-indolyl)-isoxazoline derivatives].

FTIR has been used broadly for its quick analytical rate, good reproducibility, low cost and no waste sample. The rule of infrared spectroscopic characteristics of nine 3-substituted phenyl-5-(3'-indolyl)-isoxazoline derivatives (containing phenyl and indolyl) was studied, and the influence of the substituted groups on the IR was indicated. All the 1H NMR chemical shifts of the nine novel compounds were discussed.

[Synthesis and anti-inflammatory activity of hydroxylated E,E-1-(3'-indolyl)-5-(substituted phenyl)-1,4-pentadien-3-one derivatives].

Aim: A series of new 1,4-pentadien-3-one derivatives were synthesized to search for new Eight novel hydroxylated non-steroidal anti-inflammatory drugs (NSAIDs) with potent activity.

Methods: E,E-1-(3'-indolyl)-5-( substituted phenyl)-1,4-pentadien-3-one derivatives were synthesized by means of aldol condensation and characterized by 1H NMR, ESI-MS and element analysis. Their anti-inflammatory activity in vitro were evaluated.