Synthesis and antibacterial evaluation of [S,Z]-4-methyl-2-[4-oxo-5- [[5-substituted phenylfuran-2-yl] methylene]-2-thioxothiazolidin-3-yl] pentanoic acids

The microbial resistance has become a global hazard with the irrational use of antibiotics. Infection of drug-resistant bacteria seriously threatens human health. Currently, there is an urgent need for the development of novel antimicrobial agents with new mechanisms and lower levels of toxicity. In this paper, a series of [S,Z]-4-methyl-2-[4-oxo-5-[[5-substitutedphenylfuran-2- yl] methylene]-2-thioxothiazolidin-3-yl]pentanoic acids via a Knoevenagel condensation were synthesized and evaluated for their antibacterial activity in-vitro. The synthesized compounds were characterized by IR, [1]H NMR and MS. The antibacterial test in-vitro showed that all of the synthesized compounds had good antibacterial activity against several Gram-positive bacteria [including multidrug-resistant clinical isolates] with minimum inhibitory concentration [MIC] values in the range of 2-4 micro g/mL. Especially compounds 4c, 4d, 4e and 4f were the most potent, with MIC values of 2 micro g/mL against four multidrug-resistant Gram-positive bacterial strains

Effect of Bushen Huoxue Compound on Retinal Müller Cells in High Glucose or AGEs Conditions / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the effect of Bushen Huoxue Compound (BHC) on lactate dehydrogenase (LDH) leakage, expressions of vascular endothelial growth factor (VEGF) and VEGF mRNA in retinal Muller cells under high glucose condition or advanced glycosylation end products (AGEs) condition by using serum pharmacological method.</p><p><b>METHODS</b>The retinal Müller cells of 5-7 days post-natal Sprague Dawley (SD) rats were cultured with modified enzyme-digestion method. Purified retinal Muller cells were cultured in normal conditions, high glucose condition (50 mmol/L) or AGEs (50 mg/L and 100 mg/L) conditions, and BHC-containing serum was added to culture medium. The LDH leakage and VEGF expressions were measured by enzyme-linked immunosorbent assay (ELISA). In addition, the relative expression of VEGF mRNA was tested by reverse transcription polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>Compared with the normal control group, expressions of VEGF and VEGF mRNA were significantly increased in the high glucose group, the low dose AGEs group and the high dose AGEs group (all P < 0.01). The LDH leakage was obviously increased in the high dose AGEs group, when compared with the normal control group and the high glucose group (P < 0.01). The LDH leakage, expressions of VEGF and VEGF mRNA were obviously decreased by BHC-containing serum both in high glucose and AGEs conditions (P < 0.05, P < 0.01). BHC-containing serum had no significant effect on the LDH leakage and expressions of VEGF and VEGF mRNA in normal conditions (P > 0.05).</p><p><b>CONCLUSIONS</b>AGEs intervention could obviously lower the stability of Müller cell membrane. Up-regulated expressions of VEGF and VEGF mRNA in cultured Müller cells could be induced by AGEs or high glucose. BHC-containing serum could stabilize the stability of Müller cell membrane, inhibit the transcription of VEGF mRNA and decrease the protein expression of VEGF, which might be one of important mechanisms for preventing and treating diabetic retinopathy.</p>

Synthesis and anticonvulsant evaluation of some new 6-[substituted-phenyl] thiazolo[3,2-b][l,2,4]triazole derivatives in mice

Epilepsy is the most frequent nearological affiction and afflicts 1% about of the worlds population. Currently there is an urgent need for the development of novel anticonvulsants with higher levels of potency and lower levels of toxicity. In this paper, a series of new 6-[substituted-phenyT] thiazolo[3,2-b][1.2.4]triazole derivatives were synthesized and tested for their anticonvulsant activities using the maximal electroshock [MES] and subcutaneous pentylenetetrazole [PTZ] screens, which are the most widely employed seizure models for early identification of candidate anticonvulsants. Their neurotoxicity was determined applying the rotarod test. In these compounds, 6-[4-fluorophenyl] thiazolo[3,2-b][l,2,4]triazole [3c] showed selective protection against the MES seizures with an ED[50] value of 49.1 mg/Kg and a TD[50] value of 94.1 mg/Kg, which provided compound 3c a protective index [PI = TD[50]/ED[50] of 1.9 in the MES test. 6-[4-Propoxyphenyl]thiazolo[3,2-b][l,2,4]triazole [5b] was found to be active in both models, i.e. MES test and PTZ test. In the PTZ screen, compound 5b gave an ED[50] of 63.4 mg/Kg and a TD[50] of 105.6 mg/Kg, resulting in a PI value of 1.7 which is higher than carbamazepine