Phenolic compounds from the flowers of Garcinia dulcis

Dulcisxanthones C-F and dulcinone together with 22 known compounds were isolated from the flowers of Garcinia dulcis. Their structures were determined by spectroscopic methods. The abilities of some of these compounds to act as radical scavengers and antibacterial agents were investigated.     

Synthesis and characterization of selective dopamine D2 receptor antagonists. 2. Azaindole,benzofuran, and benzothiophene analogs of L-741,626

A series of indole, 7-azaindole, benzofuran, and benzothiophene compounds have been prepared and evaluated for affinity at D_2-like dopamine receptors. These compounds share structural elements with the classical D_2-like dopamine receptor antagonists haloperidol, N-methylspiperone and benperidol. Two new compounds, 4-(4-iodophenyl)-1-((4-methoxy-1H-indol-3-yl)methyl)piperidin-4-ol (6) and 4-(4-iodophenyl)-1-((5-methoxy-1H-indol-3-yl)methyl)piperidin-4-ol (7), were found to have high affinity to and selectivity for D₂ versus D₃ receptors. Changing the aromatic ring system from an indole to other heteroaromatic ring systems reduced the D₂ binding affinity and the D₂ versus D₃ selectivity.     

Vibration activates the actin/NF‐κB axis and upregulates IL‐6 and IL‐8 expression in human periodontal ligament cells

We previously reported that mechanical vibration‐induced proinflammatory cytokines, interleukin‐6 (IL‐6) and IL‐8, expression in human periodontal ligament (hPDL) cells, however, the underlying mechanism remained unclear. Mechanical stimuli are able to activate cellular responses by inducing the activation of several signaling pathways including cytoskeletal changes and inflammation. The actin cytoskeleton is a highly dynamic network and plays many important roles in intracellular events. Here, we aimed to investigate the involvement of a pivotal mediator of inflammatory responses, nuclear factor‐κB (NF‐κB), and actin polymerization in vibration‐induced upregulation of IL‐6 and IL‐8 expression in hPDL cells. hPDL cells were pretreated with the NF‐κB inhibitor BAY 11‐7082 or cytochalasin D, respectively, before exposure to vibration. IL‐6 and IL‐8 messenger RNA (mRNA) and protein expression were quantified by quantitative polymerase chain reaction and enzyme‐linked immunosorbent assays, respectively. Subcellular localization of the NF‐κB p65 subunit was visualized by immunofluorescent staining. We found an increase in NF‐κB nuclear translocation in vibrated cells compared with control cells. Pretreatment with BAY 11‐7082 significantly inhibited vibration‐induced IL‐6 and IL‐8 mRNA and protein expression in hPDL cells. Moreover, pretreatment with cytochalasin D inhibited NF‐κB nuclear translocation and attenuated upregulation of IL‐6 and IL‐8 mRNA and protein in vibrated cells. Therefore, modulation of actin cytoskeletal polymerization in response to vibration may activate the NF‐κB signaling pathway and subsequently upregulate IL‐6 and IL‐8 expression in hPDL cells.     

Phenylpropanoid derivatives from Clausena harmandiana fruits

A new phenylpropanoid derivative, harmandianone (1), along with four known compounds: verimol B (2), (E)-3-(2-hydroxy-4-methoxy-phenyl)propanoate (3), (E)-methyl p-coumarate (4), and (E)-5-methoxy-2-(prop-1-enyl)phenol (5) was isolated from the acetone extract of Clausena harmandiana fruits. All structures were characterized by spectroscopic methods (UV, IR, NMR and ESI-TOF-MS). Compounds 1 and 3–5 demonstrated weak antibacterial activity against Escherichia coli TISTR 780, methicillin-resistant Staphylococcus aureus SK1, Salmonella typhimurium TISTR 292 and S. aureus TISTR1466, with MIC values between 64 and 128 μg/mL.     

Characterization and evaluation of two novel fluorescent sigma-2 receptor ligands as proliferation probes

We synthesized and characterized two novel fluorescent sigma-2 receptor selective ligands, SW120 and SW116, and evaluated these ligands as potential probes for imaging cell proliferation. Both ligands are highly selective for sigma-2 receptors versus sigma-1 receptors. SW120 and SW116 were internalized into MDA-MB-435 cells, and 50% of the maximum fluorescent intensity was reached in 11 and 24 minutes, respectively. In vitro studies showed that 50% of SW120 or SW116 washed out of cells in 1 hour. The internalization of SW120 was reduced ≈30% by phenylarsine oxide, an inhibitor of endocytosis, suggesting that sigma-2 ligands are internalized, in part, by an endocytotic pathway. Subcellular localization studies using confocal and two-photon microscopy showed that SW120 and SW116 partially colocalized with fluorescent markers of mitochondria, endoplasmic reticulum, lysosomes, and the plasma membrane, suggesting that sigma-2 receptors localized to the cytoplasmic organelles and plasma membrane. SW120 did not colocalize with the nuclear dye 4',6-diamidino-2-phenylindole. In vivo studies showed that the uptake of SW120 in solid tumors and peripheral blood mononuclear cells of mice positively correlated with the expression level of the cell proliferation marker Ki-67, suggesting that sigma-2 fluorescent probes may be used to image cell proliferation in mice.     

Synthesis of 2-(5-bromo-2,3-dimethoxyphenyl)-5-(aminomethyl)-1H-pyrrole analogues and their binding affinities for dopamine D2, D3, and D4 receptors

A series of 2-(5-bromo-2,3-dimethoxyphenyl)-5-(aminomethyl)-1H-pyrrole analogues was prepared and their affinity for dopamine D(2), D(3), and D(4) receptors was measured using in vitro binding assays. The results of receptor binding studies indicated that the incorporation of a pyrrole moiety between the phenyl ring and the basic nitrogen resulted in a significant increase in the selectivity for dopamine D(3) receptors. The most selective compound in this series is 2-(5-bromo-2,3-dimethoxyphenyl)-5-(2-(3-pyridal)piperidinyl)methyl-1H-pyrrole (6p), which has a D(3) receptor affinity of 4.3 nM, a 20-fold selectivity for D(3) versus D(2) receptors, and a 300-fold selectivity for D(3) versus D(4) receptors. This compound is predicted to be a useful ligand for studying the functional role of dopamine D(3) receptors in vivo.     

Synthesis and antibacterial activities of 5-hydroxy-4-amino-2(5H)-furanones

Starting from the mucohalogen acids 1a and b 5-hydroxy-2(5H)-furanones 2a-h have been prepared and tested. These novel 4-amino-5-hydroxy 2(5H)-furananones have shown a broad antibiotic activity against Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853 in the micromolar range. A one step synthesis from mucohalogen acids towards the antibacterials 2a-h was developed, in which the target was obtained from 1a and b under reflux in toluene in presence of a catalytic amount of sulfuric acid. The derivatives 2b and c displayed a MIC and MBC of 4/8mug/ml, against Staphylococcus aureus with a selectivity towards the resistant strains.     

Role of Rilpivirine and Etravirine in Efavirenz and Nevirapine-Based Regimens Failure in a Resource-Limited Country: A Cross- Sectional Study

IntroductionEtravirine(ETR) can be used for patients who have failed NNRTI-based regimen. In Thailand, ETR is approximately 45 times more expensive than rilpivirine(RPV). However, there are no data of RPV use in NNRTI failure. Therefore, we assessed the susceptibility and mutation patterns of first line NNRTI failure and the possibility of using RPV compared to ETV in patients who have failed efavirenz(EFV)- and nevirapine(NVP)-based regimens.MethodsClinical samples with confirmed virological failure from EFV- or NVP-based regimens were retrospectively analyzed. Resistance-associated mutations (RAMs) were interpreted by IAS-USA Drug Resistance Mutations. Susceptibility of ETR and RPV were interpreted by DUET, Monogram scoring system, and Stanford University HIV Drug Resistance Database.Results1,279 and 528 patients failed EFV- and NVP-based regimens, respectively. Y181C was the most common NVP-associated RAM (54.3% vs. 14.7%, p<0.01). K103N was the most common EFV-associated RAM (56.5% vs. 19.1%, P<0.01). The results from all three scoring systems were concordant. 165(11.1%) and 161(10.9%) patients who failed NVP-based regimen were susceptible to ETR and RPV, respectively (p = 0.85). 195 (32.2%) and 191 (31.6%) patients who failed EFV-based regimen, were susceptible to ETR and RPV, respectively (p = 0.79). The susceptibility of ETV and RPV in EFV failure was significantly higher than NVP failure (p<0.01).ConclusionThe mutation patterns for ETR and RPV were similar but 32% and 11% of patients who failed EFV and NVP -based regimen, respectivly were susceptible to RPV. This finding suggests that RPV can be used as the alternative antiretroviral agent in patients who have failed EFV-based regimen.     

Glycopentaphyllone: The first isolation of hydroperoxyquinolone from the fruits of Glycosmis pentaphylla

A new hydroperoxyquinolone alkaloid, glycopentaphyllone (1), along with nine compounds (2–10), was isolated from the fruits of Glycosmis pentaphylla. Their structures were elucidated on the basis of spectroscopic methods. The absolute configuration of glycopentaphyllone at C-2′ was established as S-configuration by applying Mosher's method. In addition, the completed assignments of ¹³C NMR as well as 2D NMR spectral data of compound 5 were reported herein for the first time. Also, all isolates were evaluated for antibacterial activity against Escherichia coli TISTR 780, Salmonella typhimurium TISTR 292, Staphylococcus aureus TISTR 1466, and Methicillin-resistant S. aureus SK1.