1D copper(II) and zinc(II) coordination polymers containing an unusual twisted oxalate bridge

Two new copper(II) complexes, Cu(L1)(ClO₄)₂ (1), {[(μ-oxalate)Cu(L1)] · 5H₂O}_n (2), and a zinc(II) complex, {[(μ-oxalate)Zn(L2)] · 3H₂O · 0.5DMF}_n (3) (L = 3,14-dimethyl-2,6,13,17-tetraazatricyclo[14,4,0^1.18,0^7.12]docosane), have been synthesized and characterized by X-ray crystallography. In 1, the ligand conformation is planar, and the octahedral coordination about the copper(II) ion is completed by weakly interacting ions. In 2 and 3, bridging oxalate ligands coordinate to copper(II) or zinc(II) ions in an unusually twisted bis-monodentate (trans-1,1′-bicoordination) mode.

The rigidity and steric hindrance of macrocycles L1 and L2 by the introduction of two cyclohexane rings and methyl groups on a cyclam (1,4,8,11-tetraazacyclotetradecane) skeleton cause the bridging oxalate ligands to adopt such unusual geometries in 2 and 3.     

Chemical composition and biological activities of essential oils extracted from Korean endemic citrus species

The aim of this study was to analyze the chemical composition of 14 kinds of citrus oils and to test their biological activities. Citrus essential oils were obtained by steam distillation from immature fruits collected from Jeju Island and were analyzed using gas chromatograph (GC)- flame ionization detectors (FID) and GC-MS. Limonene (55.4% to 91.7%), myrcene (2.1% to 32.1%), alpha-pinene (0.6% to 1.6%) and linalool (0.4% to 6.9%) were the major components in most citrus species. To evaluate in vitro antibacterial activity, all essential oils were tested against Propionibacterium acnes and Staphylococcus epidermidis. Nine out of fourteen citrus oils exhibited antibacterial activity against P. acnes, but not against S. epidermidis. The effects of the citrus oils on DPPH radical scavenging, superoxide radical anion scavenging, nitric oxide radical, and cytotoxicity were also assessed. Three essential citrus oils, Joadeung, Dongjunggyul, and Bujiwha, exhibited potent inhibitory effects on nitric oxide production. Two essential oils, Dongjunggyul and Joadeung, showed potent free radical scavenging activities in the DPPH assay. For future applications in cosmetic products, we also performed MTT assays in a human dermal fibroblast cell line. The majority of the essential oils showed no cytotoxicity. The results indicate that citrus essential oils can be useful natural agents for cosmetic application.     

Radiosensitization by celastrol is mediated by modification of antioxidant thiol molecules

The radiosensitizing effects of naturally occurring triterpenes were investigated in human lung cancer cells. Several quinone methide-containing triterpenes (QMTs) enhanced the cytotoxic effect of ionizing radiation (IR) and of these QMTs, celastrol (CE) had the greatest enhancing effect on IR-induced cell death in vitro. Additionally, the quinone methide moiety of CE was shown to be essential for CE-mediated radiosensitization; in contrast, dihydrocelastrol (DHCE), does not contain this moiety. Reactive oxygen species (ROS) production by IR was augmented in combination with CE, which was responsible for CE-mediated radiosensitization. CE induced the thiol reactivity and inhibited the activities of antioxidant molecules, such as thioredoxin reductase and glutathione. In vivo, nude mouse xenografting data also revealed that tumor growth delay was greater in mice treated with CE plus IR, compared with those treated with CE or IR alone. When DHCE, instead of CE, was combined with IR, tumor growth delay was similar to that in IR alone-treated mice. These results demonstrate that CE synergistically enhances the effects of IR and suggest the novel anticancer therapeutic use of CE in combination with radiation therapy.     

Novel, potent, and orally bioavailable phosphinic acid inhibitors of the hepatitis C virus NS3 protease

A potent and novel class of product-like inhibitors of the HCV NS3 protease was discovered by employing a phosphinic acid as a carboxylate isostere. The replicon activity and pharmacokinetic profile of this series of compounds was optimized by exploring the substitution of the phosphinic acid, as well as conformationally constraining these compounds through macrocyclization. The syntheses and preliminary biological evaluation of these phosphinic acids is described.     

Characterization of a novel D-lyxose isomerase from Cohnella laevoribosii RI-39 sp. nov

A newly isolated bacterium, Cohnella laevoribosii RI-39, could grow in a defined medium with L-ribose as the sole carbon source. A 21-kDa protein isomerizing L-ribose to L-ribulose, as well as D-lyxose to D-xylulose, was purified to homogeneity from this bacterium. Based on the N-terminal and internal amino acid sequences of the purified enzyme obtained by N-terminal sequencing and quantitative time of flight mass spectrometry-mass spectrometry analyses, a 549-bp gene (lyxA) encoding D-lyxose (L-ribose) isomerase was cloned and expressed in Escherichia coli. The purified endogenous enzyme and the recombinant enzyme formed homodimers that were activated by Mn(2+). C. laevoribosii D-lyxose (L-ribose) isomerase (CLLI) exhibits maximal activity at pH 6.5 and 70 degrees C in the presence of Mn(2+) for D-lyxose and L-ribose, and its isoelectric point (pI) is 4.2 (calculated pI, 4.9). The enzyme is specific for D-lyxose, L-ribose, and D-mannose, with apparent K(m) values of 22.4 +/- 1.5 mM, 121.7 +/- 10.8 mM, and 34.0 +/- 1.1 mM, respectively. The catalytic efficiencies (k(cat)/K(m)) of CLLI were 84.9 +/- 5.8 mM(-1) s(-1) for D-lyxose (V(max), 5,434.8 U mg(-1)), 0.2 mM(-1) s(-1) for L-ribose (V(max), 75.5 +/- 6.0 U mg(-1)), and 1.4 +/- 0.1 mM(-1) s(-1) for D-mannose (V(max), 131.8 +/- 7.4 U mg(-1)). The ability of lyxA to permit E. coli cells to grow on D-lyxose and L-ribose and homology searches of other sugar-related enzymes, as well as previously described sugar isomerases, suggest that CLLI is a novel type of rare sugar isomerase.     

Lymph node metastasis of gastric cancer is associated with the interaction between poly (ADP-ribose) polymerase 1 and matrix metallopeptidase 2

Poly (ADP-ribose) polymerase 1 (PARP1), which plays a critical role in the base excision DNA repair mechanism, and matrix metallopeptidase 2 (MMP2), a member of the matrix metalloprotease family, are involved in tumor formation and metastasis, respectively. In the present study, the possible association of single nucleotide polymorphisms (SNPs) and gene-gene interaction between PARP1 and MMP2 with the increased incidence of gastric cancer (GC) development and lymph node metastasis (LNM) was investigated in a Korean population. Samples were obtained from 326 patients with chronic gastritis and 153 patients with GC and genotyped using the GoldenGate? method. The PARP1 rs1136410 genotype showed a significant association with the frequency of LNM of GC (odds ratio [OR]?=?2.19, p?=?0.02), LNM stage (p?=?0.035), and tumor invasion (p?=?0.035). The allele frequency of MMP2 rs243865 was not associated with the development of GC or with the development of LNM of GC. Epistasis between the PARP1 SNP and the MMP2 SNP was associated with the development of LNM of GC. The combination of the MMP2 rs243865 CC genotype and the PARP1 rs1136410 CC or CC+CT genotypes showed a high risk of LNM of GC (OR?=?2.47, p?=?0.01; OR?=?2.28, p?=?0.01, respectively). In summary, PARP1 is associated with the risk of LNM of GC and the stage of LNM and tumor invasion. Epistasis between PARP1 rs1136410 and MMP2 rs243865 increased the risk of LNM of GC.     

Discovery of novel phosphonate derivatives as hepatitis C virus NS3 protease inhibitors

A novel class of phosphonate derivatives was designed to mimic the interaction of product-like carboxylate based inhibitors of HCV NS3 protease. A phosphonic acid (compound 2) was demonstrated to be a potent HCV NS3 protease inhibitor, and a potential candidate for treating HCV infection. The syntheses and preliminary biological evaluation of this phosphonate class of inhibitor are described.