DFT investigation of the DDQ-catalytic mechanism for constructing C-O bonds.

In this study, we investigated the photo-catalytic mechanisms for the construction of C-O bonds from arenes (benzene, 2',6'-dimethyl-[1,1'-biphenyl]-2-carboxylic acid, or 2,4-dichloro-1-fluorobenzene), catalyzed by 2,3-dichloro-5,6-dicyano--benzoquinone (DDQ). All the structures for the Gibbs free surfaces were calculated at the M06-2X-D3/ma-def2-SVP level in the SMD solvent model. Also, TDDFT calculations of DDQ were performed at the PBE1PBE-D3/ma-def2-SVP level in the SMD solvent model.

Discovery of (aza)indole derivatives as novel respiratory syncytial virus fusion inhibitors.

A new class of indole derivatives () have been identified as potent RSV fusion inhibitors. SAR exploration revealed that 5-Cl and the sulfonyl side chain of the indole scaffold are crucial for anti-RSV activity. Further optimization led to the discovery of a cyclic sulfone () with 2 nM anti-RSV activity and a much improved PK profile compared to the non-cyclic sulfone counterpart.

Discovery of Ziresovir as a Potent, Selective, and Orally Bioavailable Respiratory Syncytial Virus Fusion Protein Inhibitor.

Ziresovir (RO-0529, AK0529) is reported here for the first time as a promising respiratory syncytial virus (RSV) fusion (F) protein inhibitor that currently is in phase 2 clinical trials. This article describes the process of RO-0529 as a potent, selective, and orally bioavailable RSV F protein inhibitor and highlights the in vitro and in vivo anti-RSV activities and pharmacokinetics in animal species. RO-0529 demonstrates single-digit nM EC potency against laboratory strains, as well as clinical isolates of RSV in cellular assays, and more than one log viral load reduction in BALB/c mouse model of RSV viral infection.

Discovery of Benzoazepinequinoline (BAQ) Derivatives as Novel, Potent, Orally Bioavailable Respiratory Syncytial Virus Fusion Inhibitors.

A novel benzoazepinequnoline (BAQ) series was discovered as RSV fusion inhibitors. BAQ series originated from compound 2, a hit from similarity-based virtual screening. In SAR exploration, benzoazepine allowed modifications in the head moiety.

OsERF101, an ERF family transcription factor, regulates drought stress response in reproductive tissues.

An ERF transcription factor OsERF101 is predominantly expressed in rice reproductive tissues and plays an important role in improving rice seed setting rate under drought stress. Drought reduces grain yield due to the cumulative damage effects to plant vegetative and reproductive developmental processes. However, the genes involved in these processes are still not completely understood.

Discovery of methylsulfonyl indazoles as potent and orally active respiratory syncytial Virus(RSV) fusion inhibitors.

Recently we described a novel class of imidazopyridine compounds that showed exceptional anti-RSV potency in cell culture. However, unfavorable pharmacokinetic (PK) properties and glutathione (GSH) adduct liabilities impeded their further development. In a bid to address the PK and early safety concerns, a small compound library consisting of dozens of scaffold-hopping analogues was designed and synthesized for RSV CPE assay screening, which led to the identification of a new chemical starting point: methylsulfonyl indole compound 8.

Discovery of Piperazinylquinoline Derivatives as Novel Respiratory Syncytial Virus Fusion Inhibitors.

A novel series of piperazinylquinoline derivatives were discovered as respiratory syncytial virus (RSV) fusion inhibitors by the ligand-based screening approach. Among 3,000 hits, 1-amino-3-[[2-(4-phenyl-1-piperidyl)-4-quinolyl]amino]propan-2-ol (7) was proven to be active against the RSV long (A) strain. The anti-RSV activity was improved by converting piperidine to benzylcarbonyl substituted piperazine.

Discovery of imidazopyridine derivatives as highly potent respiratory syncytial virus fusion inhibitors.

A series of imidazolepyridine derivatives were designed and synthesized according to the established docking studies. The imidazopyridine derivatives were found to have good potency and physical-chemical properties. Several highly potent compounds such as 8ji, 8jl, and 8jm were identified with single nanomolar activities.

[Effect of NaCl stress on physiological characteristics of Physalis alkekengi var. franchetii test-tube plantlet].

Objective: To investigate the effect of NaCl stress on the growth and physiological characteristics of Physalis alkekengi var. franchetii, and to discuss the mechanism of salt tolerance.

Methods: The test-tube plantlet was cultured on the stress medium with NaCl (0.

[Study on the optimum combinations of plant hormone in callus culture of Thermopsis lanceolata].

Objective: To explore the effects of different hormone combinations on callus induction of Thermopsis lanceolata.

Methods: The effects of different hormone concentrations and ratio on callus induction and subculture multiplication of Thermopsis lanceolata were investigated by orthogonal design methods.

Results: The optimal medium of callus induction for hypocotyls explants was MS + 2, 4-D (0.

[Effects of different salt-alkaline stress on seed germination and seedling physiological characteristics of Codonopsis pilosula].

Objective: To improve salt resistance of Codonopsis pilosula seeds and seedlings under different salt-alkaline stress, the seed germination and physiological characteristics of seedlings were studied.

Methods: Several physiological indexes of Codonopsis pilosula under different salt-alkaline stress were measured, such as the germination vigor, germination rate, relative germination rate and recovery germination rate,as well as others indexes like the contents of chlorophyll, soluble protein, water and MDA and the activities of POD and SOD.

Results: The inhibitory effects of three salts on seed germination were Na2 CO3 > NaCl + Na2 CO3 > NaCl with an increased salt concentration.

[Specific anti-tumor effect of immune competent cell induced by HSP-70 of HeLa cells in vitro].

Background & Objective: Recent studies indicated that heat shock proteins (HSPs) are associated with antigenic peptides and participate in the antitumor T cell response in animals. This study was designed to investigate the mechanism of anti-tumor effect of immune competent cells (ICC) induced by HSP-70 of HeLa (cervical carcinoma) cells in vitro.

Methods: The normal peripheral blood mononuclear cells(PBMCs) stimulated with HSP-70 of HeLa cells in vitro.