Solvothermal Synthesis of Multiple Dihydropyrimidinones at a Time as Inhibitors of Eg5.

Solvothermal synthesis of multiple dihydropyrimidinones at a time has been developed in inexpensive and green bio-based solvent lactic acid without any additional catalysts or additives. By this method, thirty new dihydropyrimidinone derivatives were synthesized in two batches and characterized. All of the compounds were screened by Eg5 motor protein ATPase assay, and the positive compounds were tested against the Caco-2 cell line, HeLa cell line, L929 cell line and T24 cell line in vitro. Among them, compound C9 exhibited the best inhibitory activity against motor protein ATPase with an IC50 value of 30.25 µM and significant cytotoxic activity in the micromolar range against the cells above. The Lineweaver-Burk plot revealed that compound C9 was a mixed-type Eg5 inhibitor. A molecular modeling study using the Discovery Studio program was performed, where compound C9 exhibited good binding interaction with Eg5 motor protein ATPase, and this was consistent with the attained experimental results.

Lactic acid as an invaluable green solvent for ultrasound-assisted scalable synthesis of pyrrole derivatives.

Lactic acid has been used as a bio-based green solvent to study the ultrasound-assisted scale-up synthesis. We report here, for the first time, on the novel and scalable process for synthesis of pyrrole derivatives in lactic acid solvent under ultrasonic radiation. Eighteen pyrrole derivatives have been synthesized in lactic acid solvent under ultrasonic radiation and characterized by (1)H NMR, IR, ESI MS. The results show, under ultrasonic radiation, lactic acid solvent can overcome the scale-up challenges and exhibited many advantages, such as bio-based origin, shorter reaction time, lower volatility, higher yields, and ease of isolating the products.

Design, synthesis and molecular modeling of aloe-emodin derivatives as potent xanthine oxidase inhibitors.

A series of aloe-emodin derivatives were synthesized and evaluated as xanthine oxidase inhibitors. Among them, four aloe-emodin derivatives showed significant inhibitory activities against xanthine oxidase. The compound 4,5-dihydroxy-9,10-dioxo-9,10-dihydroanthracene-2-carbaldehyde (A1) possessed the best xanthine oxidase inhibitory activity with IC50 of 2.79 µM. Lineweaver-Burk plot analysis revealed that A1 acted as a mixed-type inhibitor for xanthine oxidase. The docking study revealed that the molecule A1 had strong interactions with the active site of xanthine oxidase and this result was in agreement with kinetic study. Consequently, compound A1 is a new-type candidate for further development for the treatment of gout.

Synthesis, biological evaluation and molecular modeling of aloe-emodin derivatives as new acetylcholinesterase inhibitors.

A series of aloe-emodin derivatives were designed, synthesized and evaluated as acetylcholinesterase inhibitors. Most of the new prepared compounds showed remarkable acetylcholinesterase inhibitory activities. Among them, the compound 1-((4,5-dihydroxy-9,10-dioxo-9,10-dihydroanthracen-2-yl) methyl) pyridin-1-ium chloride (C3) which has a pyridinium substituent possessed the best inhibitory activity of acetylcholinesterase (IC(50)=0.09 µM). The docking study performed with AUTODOCK demonstrated that C3 could interact with the catalytic active site (CAS) and the peripheral anionic site (PAS) of acetylcholinesterase.

Ethyl 3-methyl-4-oxo-4,5-dihydro-1H-pyrrolo[2,3-d]pyridazine-2-carboxyl-ate.

The title compound, C(10)H(11)N(3)O(3), was synthesized by the reaction of 3,5-bis-(ethoxy-carbon-yl)-2-formyl-4-methyl-1H-pyrrole and hydrazine hydrate. The angle between the pyrrole ring and the pyridazinone ring is 0.93 (9)°. In the crystal, inter-molecular N-H⋯O and N-H⋯N hydrogen-bond inter-actions link the mol-ecules into a two-dimensional network.

Bis[2-(1,3-dioxoisoindolin-2-yl)eth-yl] phthalate.

The title compound, C(28)H(20)N(2)O(8), was synthesized by the reaction of isobenzofuran-1,3-dione and 2-amino-ethanol in a one-pot reaction. The benzene and five-membered rings are slightly twisted to each other, making dihedral angles of 2.77 (9) and 1.77 (10)°. The rings of the phthalimide groups make dihedral angle of 57.64 (7) and 83.46 (7)° with the central benzene ring. Weak C-H⋯O, C-H⋯π and π-π [centroid-centroid distance = 3.446 (1) and 3.599 (1) Å] inter-actions reinforce the cohesion of the crystal.

Tetra-ethyl 1,1'-(ethane-1,2-di-yl)bis-(2,5-dimethyl-1H-pyrrole-3,4-dicarboxyl-ate).

The asymmetric unit of the title compound, C(26)H(36)N(2)O(8), comprises two independent mol-ecules. In each mol-ecule, the two pyrrole rings are linked by a -CH(2)CH(2)- bridge, with dihedral angles between the two pyrrole rings of 14.5 (3) and 16.4 (3)° in the two mol-ecules. Each pyrrole ring carries 2- and 5-methyl substituents and eth-oxy-carbonyl groups at the 3- and 5-positions.

[Persistent vegetative state caused by non-brain damage and its forensic assessment].

Persistent vegetative state (PVS) is described as one of the complications of brain damage in the current forensic science literatures. PVS unrelated to brain damage, however, is not uncommon in daily forensic practice. Currently, only "Assessment for Body Impairment of the Injured in Road Traffic Accident" designates PVS as one of its items under the section of "Brain, Spinal Cord, and Nerves Injury." Therefore, it is difficult to assess the damage and disability in PVS, especially PVS due to non-brain damage. Based on a case of PVS caused by chest injury in combination with relevant literature review, this paper provides a summary on the general information, etiology, pathogenesis, clinical manifestation, diagnosis and differential diagnosis of PVS, as well as a guideline for its forensic assessment.

Synthesis, structure and antibacterial activity of novel 1-(5-substituted-3-substituted-4,5-dihydropyrazol-1-yl)ethanone oxime ester derivatives.

A series of novel 1-(5-substituted-3-substituted-4,5-dihydropyrazol-1-yl)ethanone oxime ester derivatives are synthesized. The results show that compounds 14 and 26c can strongly inhibit Staphylococcus aureus DNA gyrase and Escherichia coli DNA gyrase (with IC(50) of 0.25 and 0.125 microg/mL against S. aureus DNA gyrase, 0.125 and 0.25 microg/mL against E. coli DNA gyrase). On the basis of the biological results, structure-activity relationships are also discussed.

1,4,8,11-Tetra-kis(carboxy-meth-yl)-5,5,7,12,12,14-hexa-methyl-4,11-diaza-1,8-diazo-niacyclo-tetra-decane dichloride dihydrate.

The title compound, C(24)H(46)N(4)O(8) (2+)·2Cl(-)·2H(2)O, was synthes-ized by the hydrolysis of tetra-ethyl 2,2',2'',2'''-(5,5,7,12,12,14-hexa-methyl-1,4,8,11-tetra-azacyclo-tetra-decane-1,4,8,11-tetra-yl) tetra-acetate in hydro-chloric acid solution. The crystal structure of the title compound consists of a 14-membered C(10)N(4) centrosymmetric cationic macrocycle which inter-acts with the chloride ions and water mol-ecules of crystallization to give a three-dimensional hydrogen-bonded network.