Synthetic and antibacterial studies on some new furanopeptides

A series of new furanopeptides (3) are prepared by the coupling of arylsubstituted furoic acids (1) with amino acid methyl esters, di and tetra-peptide methyl esters using dicyclohexyl carbodiimide (DCC) as coupling agent. Some of the newly synthesized compounds are characterized on the basis of IR, 1H NMR, mass spectral data and elemental analysis. Some of the selected compounds are also tested for their antibacterial properties.     

In vitro release studies of chlorpheniramine maleate from gels prepared by different cellulose derivatives

The objective of this study was to evaluate the in vitro and ex vivo percutaneous absorption of chlorpheniramine maleate (CPM) from different hydrogel formulations. Various concentrations of polymers, including hydroxypropylmethylcellulose (HPMC), sodium carboxymethylcellulose (NaCMC) and methyl cellulose (MC) were used in the hydrogel formulations. All experiments were conducted using cellulose dialysis membrane. The passive permeation of CPM was affected by the polymer concentrations. The effect of each polymer on the release rate of CPM was found to be statistically different (P<0.05). The formulation which exhibited maximum drug release through cellulose membrane was then used with other membranes namely polyurethane membrane, rat skin and human skin. The release rate of CPM from different membranes was found to be statistically different (P<0.05). Within the different diffusional barriers rat skin was found to be best alternative to human skin. It seems suitable the use of cellulose derivatives for topical application of CPM to obtain high therapeutic concentration at the application site. The synthetic membranes can be used to assess product performance in quality assurance but give little indication of its performance ex vivo.     

A randomized controlled trial of a new ovule formulation of ornidazole for the treatment of bacterial vaginosis

OBJECTIVE: To compare the efficacy of 500 mg ornidazole vaginal ovules (VO) and vaginal tablets (VT) in the treatment of bacterial vaginosis. METHOD: Patients were allocated at random to one group of 50 subjects to be treated with a VO (500 mg) prepared in our laboratory and to a second group of 50 subjects to be treated with a VT of ornidazole (500 mg). Therapeutic efficacy was assessed by Nugent's scoring system and clinical criteria (Amsel's criteria) before and 1 week after treatment. RESULTS: At the first follow-up visit, complete disappearance of the signs and symptoms or highly significant reduction in intensity of symptoms was observed in both treatment groups. No significant difference was evident between the two ornidazole formulations.     

Liver fibrosis attributed to lipid lowering medications: two cases

We identified two cases of chronic active hepatitis with liver fibrosis induced by lipid lowering drugs of the statin and fibrate classes despite regular monitoring of transaminases. There are few reports of clinically significant hepatitis induced by these drugs and even fewer cases of fibrosis. Given the growing use of these drugs, there are implications for monitoring patients on long-term therapy for liver damage.     

Design,synthesis, and antimalarial evaluation of thiazole-derived amino acids

A series of thiazole-derived N-Boc amino acids were synthesized and evaluated as targeted potential antimalarials against plasmepsins II enzyme of malaria parasite Plasmodium falciparum. All the compounds showed moderate to good activity. Compounds 3f and 3g were found to have highest the 50% inhibitory concentration (IC₅₀) values (3.45 μM and 4.89 μM, respectively) against Plasmodium falciparum. The compounds docked to the active site of plasmepsin II. Most of the compounds were found to interact with the catalytic amino acids ASP34 and ASP214 of plasmepsin II. A good correlation was observed between binding energy and antiparasitic activity of the thiazole derivatives.     

双氢青蒿素对恶性疟原虫有性生殖期的影响

Eighteen falciparumn malaria patients with gametocytemia were randomly allocated to 2 groups,treated respectively with dihydroartemisinin (DATM) tablets at a total dose of 360 mg over 5 days and with oral quinine sulfate (QN) at a total dose of 10 5000 mg over 7 days. Peripheral gametocyte counts were done daily in all patients until its disappearance. Blood samples were taken on D0, D4, D7, D10, D14, D21 and D28 from the patients to perform infectivity tests to Anopheles dirus. The result showed that the mean clearance times of PFG were 21.8±5.2 days in DATM group and 31.5±8.7 days in QN group respectively. And in DATM group, the infectivity tests were positive in 6 cases only. In those 6 positive cases, the numbers of the positive infectivity on D4, D7, D10, D14 and D21 were 6/6,6/6,2/6,0/6 and 0/6 respectively. While the 4 negative cases on D0 remained negative infectivity on D4, D7, D10, D14. In QN group, the infectivity tests were positive in 4 cases too on D0, the numbers of positive cases on D4, D7, D10, D14, D21 and D28 were 8/8,8/8,8/8,8/8,2/8 and 0/8 respectively. These indicate that QN cannot inhibit P.Falciparum at sexual stage, while DATM has a remarkable inhibitory effect, and may prevent the immatured PFG that was failure to infect An. dirus on D0 from maturing.     

UC 84及其衍生物的合成

合成了化合物２－氯－５－（５,６－二基－１,４－氧硫杂环己二烯－３－甲酰氨基）苯甲酸异丙酯（ＵＣ８４）,并以其为先导物合成了１１个未见报道的衍生物,活性筛选表明该类化合物有明显的抗单纯疱疹病毒（ＨＳＶ）和乙肝病毒（ＨＢＶ）活性。     

3D QSAR studies on new piperazine derivatives with antihistamine and antibradykinin effects

Three dimensional QSAR studies for antihistamine and antibradykinin effects of new piper azine derivatives were conducted using the comparative molecular field analysis. Electro static and steric factors, but not hydrophobic factor, of the synthesized compounds were correlated with the antagonistic effect.     

Chemical constituents from Qianliang tea

Ten compounds were isolated from Qianliang tea, a kind of dark tea fully fermented from the leaves of Camellia sinensis (L.) O. Kuntze var. sinensis, and identified as N-(2-hydroxyphenyl)-2-pyrrolidinone (1), p-hydroxyacetophenone (2), salicifoliol (3), (-)-3-hydroxy-β-ionone (4), p-hydroxy ethyl cinnamate (5), ethyl 4-(sulfooxy)benzoate (6), (+)-matairesinol (7), (-)-pinoresinol (8), (+)-lirioresinol-A (9), and caffeine (10), among which compound 1 was isolated as a new natural product, and compound 6 was isolated from Theaceae family for the first time. Compounds 3, 4, 5, 7, 8, and 9 were isolated from this species for the first time.     

Inhibition of acetylcholinesterase by two genistein derivatives: kinetic analysis,molecular docking and molecular dynamics simulation

In this study two genistein derivatives (G1 and G2) are reported as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), and differences in the inhibition of AChE are described. Although they differ in structure by a single methyl group, the inhibitory effect of G1 (IC₅₀=264 nmol/L) on AChE was 80 times stronger than that of G2 (IC₅₀=21,210 nmol/L). Enzyme-kinetic analysis, molecular docking and molecular dynamics (MD) simulations were conducted to better understand the molecular basis for this difference. The results obtained by kinetic analysis demonstrated that G1 can interact with both the catalytic active site and peripheral anionic site of AChE. The predicted binding free energies of two complexes calculated by the molecular mechanics/generalized born surface area (MM/GBSA) method were consistent with the experimental data. The analysis of the individual energy terms suggested that a difference between the net electrostatic contributions (ΔE_ele+ΔG_GB) was responsible for the binding affinities of these two inhibitors. Additionally, analysis of the molecular mechanics and MM/GBSA free energy decomposition revealed that the difference between G1 and G2 originated from interactions with Tyr124, Glu292, Val294 and Phe338 of AChE. In conclusion, the results reveal significant differences at the molecular level in the mechanism of inhibition of AChE by these structurally related compounds.KEY WORDS: Genistein derivatives, Acetylcholinesterase (AChE), Kinetics analysis, Molecular docking, Molecular dynamics simulation, MM/GBSAAbbreviations: ACh, acetylcholine; AChEIs, acetylcholinesterase inhibitors; AChE, acetylcholinesterase; AD, Alzheimer׳s disease; BuChE, butyrylcholinesterase; BuSCh, S-butyrylthiocholine chloride; CAS, catalytic active site; DTNB, 5,5′-dithiobis-(2-nitrobenzoic acid); GAFF, generalized AMBER force field; G1, 3-(4-methoxyphenyl)-7-(2-(piperidin-1-yl)ethoxy)-4H-chromen-4-one; G2, (S)-3-(4-methoxyphenyl)-7-(2-(2-methylpiperidin-1-yl)ethoxy)-4H-chromen-4-one; iso-OMPA, tetraisopropyl pyrophosphoramide; MD, molecular dynamics; MM/GBSA, molecular mechanics/generalized born surface area; PAS, peripheral anionic site; PDB, protein data bank; PME, particle mesh Ewald; RMSD, root-mean-square deviation; S-ACh, acetylthiocholine iodide; ΔE_ele, electrostatic energy contribution; ΔE_MM, gas-phase interaction energy between receptor and ligand; ΔE_vdw, van der Waals energy contribution; SASA, solvent accessible surface area; ΔG_exp, experimental binding free energy; ΔG_GB, polar desolvation energy term; ΔG_pred, total binding free energy; ΔG_SA, nonpolar desolvation energy term; ΔS, conformational entropy contribution