Synthesis and Neuroprotective Activity of Novel C4, C7 Derivatives in Tetracycline Series

Since the discovery of the tetracycline in 1953, numerous natural andsemisynthelic tetracyclines have been reported with broad spectrum antibacterial activity .Doxycycline 1 and minocycline 2 are semisyn-thetic second-generation tetracyclines that exertanti-inflammatory effects. These effects appear completely separate and distinct fromtheirantimicrobial actio. Minocycline and doxycycline are absorbed rapidly and show higher brainpenetrability than other tetracyclines. During recent years, doxycycline and minocycline have shownto have neuroprotective effects in models of global and focal ischemia . The neuroprotective effectsare assumed to result from the inhibition of microglia activation. Furthermore, from an in vitrostudy, it was reported that minocycline induces neuroprotection against NMDA-induced neurotoxicityby inhibiting p38 MAP ki-nase activity in microglia . However, neuroprotective mechanisms andstructure-activity relationships of these compounds in neurons are unclear.

Differentiation of Constitutional Isomer of 2,2a,3,4-Tetrahydro- 4-methyl-2a-phenyl-2-(thiophen-2-yl)-1H-azeto[2,1-d][1,5] benzothiazepin-1-one-5-oxide and Fragmentations of 2,3-Dihydro- 2,4-diphenyl-1,5-benzothiazepine-1-oxide/-1,1-dioxide

Mass spectrometric behaviour of 2,2a,3,4-tetrahydro-4-methyl-2a-phenyl-2-(thiophen-2-yl)-1H-azeto[2,1-d][1,5]benzothiazepin-1-one-5-oxide and 2,3-dihydro-2,4-diphenyl-1,5-benzothiazepine-1-oxide/-1,1-dioxide have been studied with the aid of mass-analyzed ion kinetic energy spectrometry and accurate mass measurements under electron impact ionization. The monooxide derivatives showed a tendency to eliminate an alkene or an oxygen atom. 1H-Azeto[2,1-d][1,5]benzothiazepin-1-one-5-oxide could also eliminate the thiophen-2-ylketene molecule via a reverse [2+2] cycloaddition. 2,3-Dihydro-2,4-diphenyl-1,5-benzothiazepine-1-oxide/-1,1-dioxide could eliminate SO_2 or SO, respectively. The structure of 2,2a,3,4-tetrahydro-4-methyl-2a-phenyl-2-(thiophen-2-yl)-1H-azeto[2,1-d][1,5]benzothiazepin-1-one-5-oxide was identified on the basis of its fragmentation. The identification was supported by the fragmentations of model compound, 2,3-dihydro-2,4-diphenyl-1,5-benzothiazepine-1-oxide/-1,1-dioxide.

The Different Fluorescent Response of Quin 2 to the Binding of Ca^(2+) and La^(3+) and its Application

The fluorescence spectra of Quin 2, (2-[(2-bis-[carboxymethyl] amino-5-methylphenoxy) methyl]-6-methoxy-8-bis [carboxymethyl] aminoquiniline), a Ca2+ probe, were investigated upon incubation with Ca2+ or La3+. The results showed that binding of La3+ to Quin 2 resulted in different fluorescent spectrum from that of Ca2+. Based on this observation, a fluorescent method was developed for simultaneously determination of the dissociation rates of Ca2+ and La3+ from a Ca-La- calmodulin complex (Ca2La2CaM).

Molecular Spectroscopic Study on the Interaction between Heparinand Neutral Red

The interaction between heparin and neutral red was investigated by molecular spectroscopic methods. The change of all spectra suggested that positively charged neutral red had interacted with negatively charged heparin. The study of influence factors indicated that electrostatic force and hydrophobic bond might be involved in the interaction. The total binding number per disaccharide unit and intrinsic binding constant were obtained using Scatchard model.

An Efficient and Mild Preparation of Vinyl Diazo Carbonyl Compounds

The combination of (CF3CO)2O/Et3N is found to be a mild and efficient dehydration condition for β-hydroxy-α-diazo compounds.

Diastereoselective α-Alkylation of β-Amino Esters: Preparation of Novel α-Substituted β-Amino Esters from α-Amino Acids

Enantiomerically pure a-substituted bamino esters were prepared from natural L-a-amino acids through Arndt-Eistert homologation and diastereoselective aalkylation.

Inhibition of nicotine-DNA adduct formation by polyphenolic compounds in vitro

Nicotine [3-(1-methyl-2-pyrrolidinyl)-pyridine], a major alkaloid in tobacco products, has proven to be a potential genotoxic compound. Some polyphenolic compounds can suppress the DNA adduction, and hence act as the potential inhibitors of carcinogenesis. In this study, the inhibitory effects of three polyphenolic compounds, curcumin (diferuloylmethane), resveratrol (trans-3, 5, 4-trihydroxystilbene) and tea polyphenols, on the nicotine-DNA adduction have been investigated in vitro using radiolabelled nicotine and liquid scintillation counting (LSC) technique. Also, the inhibition mechanism of these chemopreventive agents in regard to the activity of the biotransformation enzymes, including cytochrome P450 (CYP450), cytochrome b5 (CYb5) and glutathione S-transferase (GST), has been studied. The results demonstrated that these three polyphenols induced marked dose-dependent decrease in nicotine-DNA adducts as compared with the controls. The elimination rate of adducts reached above 46% at the highest dose for all the three agents with 51.6% for resveratrol. Correspondingly, three polyphenols all suppressed CYP450 and CYb5, whereas curcumin and resveratrol induced GST. We may arrive at a point that the three polyphenols are beneficial to prevent the nicotine adduct formation, and thus may be used to block the potential carcinogenesis induced by nicotine.

Reactions of Imidates with Phenoxyacetyl Chloride

The reactions of imidates including cyclic imidates, oxazolines and dihydrooxazine with phenoxyacetyl chloride, were investigated. The results indicate that diacylamide or acylamide was generated from N-phenoxyacetylated imidates, while cyclic imidate oxazolines underwent a ring-opening reaction to yield different amides depending on the reaction conditions. Even under non-nucleophilic conditions, no β-lactam-fused oxazoline derivative was obtained.

Catalytical Activities of Reconstructed Hemoglobin with Different Central Ions in Prosthetic Group

Hemoglobin(Hb) was de-prosthetized, which was then reconstructed with the prosthetic groups with different central metal ions including Fe(Ⅲ), Co(Ⅱ) and Mn(Ⅱ). The spectral properties along with the catalase and peroxidase activities of the reconstructed hemoglobin were compared with those of Hb and prosthetic groups with different ions. When the central ion is iron, the reconstituted Hb(rHb) has the highest catalase and peroxidase activities. Maybe it is the reason that iron is chosen as the central ion in the prosthetic groups of natural hemoproteins. Different from peroxidase activity, the catalase activity of hemin cannot be enhanced by the microenvironment of apoHb. This result shows that the structure of apoHb is more similar to that of apoHRP than that of apocatalase.

An Unusual Reductive Ring-opening Reaction of Phthalimide with Sodium Hydride in DMF

An unusual reductive ring-opening reaction of phthalimide with sodium hydride in anhydrous DMF was observed for the first time. The presumed mechanism was described in detail.

Assembly of a Library of Trisaccharides as Mimics of Sialyl Lewis Xvia Random Combination Strategy

A small library containing six positional isomers of fucosyl on the modified lactoside backbone as mimics of the Sialyl Lewis X was synthesized via random combinatorial glycosylation, which was charactered by ESI-MS and HPLC.

Synthesis of RGD-aPEG-lactoside, a Potential Anti-metastasis Glycoconjugate

The adhesive interaction between tumor cells and host cells or the extra cellular matrix plays a crucial role in metastasis. Due to the anti-metastasis effects of RGD (arginyl-glycyl -aspartic acid) and some oligosaccharides, RGD-aPEG-Lactoside was prepared which will be used on anti-metastasis.

Mass Spectrometry of 2a,4-Disubstituted 5-Benzoyl-2a,3,4,5-tetrahydro-2-phenoxy-azeto[1,2-a][1,5]benzodiazepin-1(2H)-ones Under Electron Impact Ionization Conditions

The mass spectrometric fragmentation of 2a,4-disubstituted 5-benzoyl-2a,3,4,5-tetrahydro-2-phenoxy-azeto{[1,2-a]}[1,5]benzodiazepin-1(2H)-ones has been investigated by means of mass-analyzed ion kinetic energy spectrometry under electron impact ionization conditions. All compounds tend to lose different moieties, such as phenoxy, phenoxy and H, and phenoxyketene. Both [M +-PhO] and [M +-PhOH] ions could further lose CO, and the [M +-PhOCHCO] ions could lose propene or styrene, PhCON, PhCOHN, and other fragments.

The Purification of Glucose Type Glycosyl Nitrate and the Synthesis of Spacer-armed N-Acetyllactosamines and Their Dimers

di-O-acetyl-4-O-(2, 3, 4, 6-tetra-O-acetyl-b-D-galactopyranosyl)-2-azido-2-deoxy- b-D-glucoppyranosyl nitrate could be separated from its mannose type isomer by glycosylation according to the reactivity difference of these two compounds. The pure glucose type nitrate can be converted to corresponding trichloroacemidate, which reacted with spacer arms in solution of CH2Cl2 with BF3稥t2O as promoters to give desired glycosides and dimers.

Synthesis of a Novel Conjugate of Dibenzoyldiazomethane and Polyamide Containing N-Methylimidazoles

A novel conjugate of dibenzoyldiazomethane and polyamide containing N-methylimida-zoles was synthesized by a chloroform reaction and a DCC/HOBT coupling reaction.

A Convenient Method for the Synthesis of Distamycin Analogue

A novel distamycin analogue was synthesized by chloroform reaction and DCC / HOBT coupling reaction without using amino protection and deprotection.

Synthesis of Asymmetric Propanetriol Analogues

From natural tartaric acid, (R)-2-benzyloxy-3-(2-tetrahydropyranyloxy) propanol 3 was designed and synthesized, and (R)-2-benzyloxy-3-(4-methoxybenzyloxy) propanol 7 was prepared in a new method. They can be used as chiral synthons of lysophosphatidic acid and other compounds with asymmetric propanetriol backbone.

Trafficking of α1B-adrenergic receptor mediated by inverse agonist in living cells

AIM The project is aimed at understanding the action of inverse agonist at single molecule level and capturing the real time picture of molecular behavior of α1B-adrenergic receptor (AR) mediated by inverse agonist in living cells by single molecule detection (SMD). METHODS The location and distribution of α1B-AR was detected by laser confocal and whole cell ^3H-prazosin binding assay. Dynamic imaging of BODIPY-FL-labeled prazosin (Praz), specific antagonist of (1-AR, was observed in α1B-AR stably expressed human embryonic kidney 293 (HEK293) living cells. The detection of real-time dynamic behaviors of AR was achieved by using fluorescence-labeled AR and its ligand combined with SMD techniques. RESULTS α1B-AR was predominantly distributed on the cell surface and 8.2% of the total receptors were located in cytosol.

Effects of the rare earth ions on bone resorbing function of rabbit mature osteoclasts in vitro

The effects of rare earth ions on bone resorbing function of osteoclasts were studied by culturing Japanese white rabbit osteoclasts on bone slices. In order to evaluate the activity of osteoclasts, the number and surface areas of lacunae were measured by photomicrography and image analysis, and the calcium concentration in the supernatant was measured by the atomic absorption spectrometry. The lacunae morphology was observed under a scanning electron microscope. The results indicated that La3+, Sm3+ and Er3+ at the concentration of 1.00?0-5, 1.00?0-6 and 1.00?10-7mol/L and Nd3+, Gd3+ and Dy3+ at the concentration of 1.00?10-5 and 1.00?0-6 mol/L inhibited osteoclastic activity as indicated by the dose-dependent reduction in the numbers and surface areas of the lacunae (P<0.01). On the contrary, the number and surface areas of lanunae were increased and osteoclastic bone resorbing function was significantly enhanced by La3+, Sm3+ and Er3+ at the concentration of 1.00?0-8 mol/L and Nd3+, Gd3+ and Dy3+ at the concentration of 1.00?0-7 mol/L (P<0.01). Nd3+, Gd3+ and Dy3+ had no effect on osteoclastic bone resorption function at concentrations as low as 1.00?0-8 mol/L (P>0.05). It is suggested that the effects of rare earth ions on osteoclastic bone resorption are bidirectional, depending on concentrations and species.