Zhongyuan Wu

Synthesis and anticonvulsant activity of new 6-methyl-1-substituted-4,6-diazaspiro[2.4]heptane-5,7-diones.

In the present study on the development of new anticonvulsants, twenty new 6-methyl-1-substituted-4,6-diazaspiro[2.4]heptane-5,7-diones were synthesized and tested for anticonvulsant activity using the maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) screens. Their neurotoxicity was determined by the rotorod test. In this series, all of the alkyl- and aryl-substituted 5,5-cyclopropanespirohydantoins showed more or less protection against MES and/or scPTZ models. The most active of the series was 6-methyl-1-(4-(methylsulfonyl)phenyl)-4,6-diazaspiro[2.4]heptane-5,7-dione (6 t), which showed a MES ED(50) value of 12.5 mg/kg in mice. The median toxic dose (TD(50)) was 310 mg/kg, providing compound 6 t with a protection index (PI = TD(50)/ED(50)) of 24.8 in the MES test which is better than phenytoin.

Synthesis, characterization and biological evaluation of some 16E-arylidene androstane derivatives as potential anticancer agents.

A series of new 16E-arylidene androstane derivatives were synthesized and characterized. The new compounds were screened for their anticancer activities against the human cancer cell lines SW480, A549, HepG2 and HeLa in vitro using the MTT assay. The results of the in vitro study showed that a number of compounds have shown IC(50) values lower than 20 μM against the four cancer cell lines.

Synthesis, characterization and biological evaluation of some 16β-azolyl-3β-amino-5α-androstane derivatives as potential anticancer agents

A series of new 16β-azolyl-3β-amino-5α-androstane derivatives were synthesized and characterized. The new compounds were screened for their anticancer activity against the human cancer cell lines SW480, A549, HepG2, HeLa and SiHa in vitro using the MTT assay. The results of the in vitro study showed that a number of compounds have shown IC(50) values lower than 20 μM against the five cancer cell lines.

Synthesis and anticonvulsant activity of N-3-arylamide substituted 5,5-cyclopropanespirohydantoin derivatives.

In the present study on the development of new anticonvulsants, twenty new N-3-arylamide substituted 5,5-cyclopropanespirohydantoin derivatives were synthesized and tested for anticonvulsant activity using the maximal electroshock (MES), subcutaneous pentylenetetrazole (scPTZ) screens, which are the most widely employed seizure models for early identification of candidate anticonvulsants. Their neurotoxicity was determined applying the rotorod test. Three compounds 5d, 5j and 5t showed promising anticonvulsant activities in both models employed for anticonvulsant evaluation. The most active compound 5j showed the MES-induced seizures with ED50 value of 9.2 mg/kg and TD50 value of 421.6 mg/kg after intraperitoneally injection to mice, which provided compound 5j with a protective index (TD50/ED50) of 45.8 in the MES test.

Synthesis and Anticonvulsant Activity of 1‐(2‐(8‐(benzyloxy)quinolin‐2‐yl)‐1‐butyrylcyclopropyl)‐3‐Substituted Urea Derivatives

In the present study on the development of new anticonvulsants, 16 new1‐(2‐(8‐(benzyloxy)quinolin‐2‐yl)‐1‐butyrylcyclopropyl)‐3‐substituted urea derivatives were synthesized and tested for anticonvulsant activity using the maximal electroshock seizure, subcutaneous pentylenetetrazole screens, which are the most widely employed seizure models for early identification of candidate anticonvulsants. Their neurotoxicity was determined by applying the rotorod test. Three compounds 7a, 7e, and 7m showed promising anticonvulsant activities in both models employed for anticonvulsant evaluation. The most active compound 7e showed the maximal electroshock seizure‐induced seizures with ED50 value of 14.3 mg/kg and TD50 value of 434 mg/kg after intraperitoneal injection to mice, which provided compound 7e with a protective index (TD50/ED50) of 30.3 in the maximal electroshock seizure test.

16-morpholino quaternary ammonium steroidal derivatives as neuromuscular blocking agents: synthesis, biological evaluation and in silico probe of ligand-receptor interaction.

A series of steroidal 3,16-bis-quaternary ammonium salts were synthesized and screened on mouse hemi-diaphragm to explore new steroidal neuromuscular blocking agents. There were two compounds, 3β-piperidino derivate 8d (IC(50) = 3.49 μM) and 3β-N-methylbenzylamino derivate 8g (IC(50) = 4.54 μM), showing activity close to rocuronium (IC(50) = 2.50 μM). The preliminary structure-activity relationship was deduced from the bioactivity results with the aid of the calculated N-N distance and log P. Meanwhile, the interactions between the ligand and binding pocket were revealed by docking 8d to the ligand binding domain of the mouse muscle nicotinic acetylcholine receptor (nAChR). This nAChR was modeled using Molecular Operating Environment (MOE) package indirectly from mollusca acetylcholine binding protein with mouse neuron α7 nAChR as intermediary template.

Synthesis and anticonvulsant activity of ethyl 1-(2-arylhydrazinecarboxamido)-2,2-dimethylcyclopropanecarboxylate derivatives

In the present study on the development of new anticonvulsants, twenty three 1-(2-arylhydrazinecarboxamido)-2,2-dimethylcyclopropanecarboxylate derivatives were synthesized and tested for anticonvulsant activity using the maximal electroshock (MES), subcutaneous pentylenetetrazole (scPTZ) screens, which are the most widely employed seizure models for early identification of candidate anticonvulsants. Their neurotoxicity was determined applying the rotorod test. Three compounds 6g, 6m and 6w showed promising anticonvulsant activities in both models employed for anticonvulsant evaluation. The most active compound 6m showed the MES-induced seizures with ED(50) value of 9.8 mg/kg and TD(50) value of 332.2 mg/kg after intraperitoneally injection to mice, which provided compound 6m with a protective index (TD(50)/ED(50)) of 33.9 in the MES test.

Chemical composition and antioxidant activity of the essential oil of endemic Viola tianshanica

The composition and in vitro antioxidant activities of the essential oil and methanol extract of the aerial parts of Viola tianshanica were evaluated in this research. GC–MS analysis of the essential oil resulted in the identification of 15 constituents, representing 89.67% of the oil. The major compounds detected in the essential oil were dibutyl phthalate (15.19%), hexadecanoate methyl (8.65%), n-hexadecanoic acid (3.07%) and 2,3-pentanedione (2.62%). Essential oil and methanol extract were tested for their antioxidant activities using 1,1-diphenyl-2-picryl-hydrazyl free radical scavenging and β-carotene linoleic acid assay. In addition, the total phenol of essential oil, polar subfraction and non-polar subfraction were determined.

Synthesis and antibacterial activity of 3-O-carbamoyl derivatives of 6,11-di-O-methylerythromycin A: a novel class of acylides.

A novel series of acylides, 3-O-carbamoyl derivatives of 6,11-di-O-methylerythromycin A, were synthesized and evaluated for their antibacterial activity. These compounds have significant antibacterial activity against gram-positive pathogens, including erythromycin-resistant but methicillin-susceptible Staphylococcus aureus, erythromycin-resistant and methicillin-resistant S. aureus, erythromycin-resistant Streptococcus pneumoniae, and gram-negative pathogens, such as Haemophilus influenzae. Among the derivatives tested, compounds 4p, 4r, 4w, 4x and 4z were found to have potent activity against most susceptible and resistant bacteria. Compound 4p exhibited excellent antibacterial activity in comparison to the others.

Synthesis and antibacterial activity of novel 4 -carbamates of 6,11-di-O-methylerythromycin A

A novel series of 4″-carbamates of 6,11-di-O-methylerythromycin A were synthesized and evaluated. These compounds have significant antibacterial activity against Gram-positive pathogens, including erythromycin-resistant but methicillin-susceptible Staphylococcus aureus, erythromycin-resistant and methicillin-resistant Staphylococcus aureus, erythromycin-resistant Streptococcus pneumoniae and Gram-negative pathogens, such as Haemophilus influenzae To our surprise, most of the derivatives tested had potent activity against most resistant bacteria. Among these, compounds 10u, 10v, 10w and 10y were found to have potent activity against most susceptible and resistant bacteria. In particular, compound 10y exhibited excellent antibacterial activity in comparison to others.