A Bis-Cyclopentadienyl Ligand-Supported Di-Iron Trihydride Motif as a Synthon for Access to Heterobimetallic Trinuclear Complexes.

Herein, we report the synthesis of a flexible bis-cyclopentadienyl ligand L (the doubly deprotonated form of H2L (1,3-bis(2,4-di-tert-butylcyclopentadienyldimethylsilyl)benzene)), demonstrating its ability to stabilize a series of di-iron hydrido complexes. Notably, this ligand facilitates the isolation of an unprecedented anionic cyclopentadienyl ligand-supported di-iron trihydride complex, LFe2(µ-H)3Li(THF) (2), functioning as a synthon for the [Fe2(µ-H)3]- core and providing access to heterobimetallic complexes 4-6 with coinage metals.

Access to Monomeric Lead(II) Hydrides with Remarkable Thermostability and Their Use in Catalytic Hydroboration of Carbonyl Derivatives.

We report on the remarkable stability of unprecedented, monomeric lead(II) hydrides M+[LPb(II)H]- (M[1-H]), where L = 2,6-bis(3,5-diphenylpyrrolyl)pyridine and M = (18-crown-6)potassium or ([2.2.2]-cryptand)potassium. The half-life of [K18c6][1-H] of ∼2 days in tetrahydrofuran at 25 °C is significantly longer than those reported for dimeric lead(II) hydrides supported by bulky terphenyl ligands (few hours at low temperatures), which are the only examples known for lead(II) hydride compounds. The presence of a Pb-H bond in [1-H]- was unambiguously identified by multinuclear NMR spectroscopy. Remarkably, a 1H resonance of the hydride ligand was found at δ = 41.43 ppm (1JPbH = 1312 Hz). For reactivity study, [1-H]- serves as an excellent hydroboration catalyst with high turnover numbers and turnover frequencies for several carbonyl compounds.

Gait-Based Machine Learning for Classifying Patients with Different Types of Mild Cognitive Impairment.

Mild cognitive impairment (MCI) may be caused by Alzheimer's disease, Parkinson's disease (PD), cerebrovascular accident, nutritional or metabolic disorders, or mental disorders. It is important to determine the cause and treatment of dementia as early as possible because dementia may appear in remission. Decline in MCI cognitive function may affect a patient's walking performance. Therefore, all participants in this study participated in an experiment using a portable gait analysis system to perform walk, time up and go, and jump tests. The collected gait parameters are used in a machine learning classification model based on a support vector machine (SVM) and principal component analysis (PCA). The aim of the study is to predict different types of MCI patients based on gait information. It is shown that the machine learning classification model can predict different types of MCI patients. Specifically, the PCA-SVM model demonstrated better classification performance with 91.67% accuracy and 0.9714 area under the receiver operating characteristic curve (ROC AUC) using the polynomial kernel function in classifying PD-MCI and non-PD-MCI patients.

Skeletally Diverse Synthesis of Innovative [2,1-c]-1,4-Oxazepine and [1,4]-Quinoxaline Systems.

An efficient, innovative synthesis of [2,1-c]-1, 4-oxazepine and [1,4]-quinoxaline heterocycles along with the embodied pyrimido-pyrrolo motifs was established. Initially, the pyrrole ring was installed using microwave irradiation through an intramolecular base-catalyzed cyclization between acetyl bromomethyl pyrimidine dione and o-amino phenyl methanol or o-phenylenediamine methyl benzoates. Furthermore, oxazepine, and quinoxaline scaffolds were constructed by an acid-catalyzed condensation with a variety of aldehydes by an unconventional Pictet-Spengler reaction strategy. An important aspect of this work is to build novel heterocyclic ring systems with potential medicinal interest.

Synthesis and inhibitory effects of novel pyrimido-pyrrolo-quinoxalinedione analogues targeting nucleoproteins of influenza A virus H1N1.

The influenza nucleoprotein (NP) is a single-strand RNA-binding protein and the core of the influenza ribonucleoprotein (RNP) particle that serves many critical functions for influenza replication. NP has been considered as a promising anti-influenza target. A new class of anti-influenza compounds, nucleozin and analogues were reported recently in several laboratories to inhibit the synthesis of influenza macromolecules and prevent the cytoplasmic trafficking of the influenza RNP. In this study, pyrimido-pyrrolo-quinoxalinedione (PPQ) analogues as a new class of novel anti-influenza agents are reported. Compound PPQ-581 was identified as a potential anti-influenza lead with EC50 value of 1 µM for preventing virus-induced cytopathic effects. PPQ produces similar anti-influenza effects as nucleozin does in influenza-infected cells. Treatment with PPQ at the beginning of H1N1 infection inhibited viral protein synthesis, while treatment at later times blocked the RNP nuclear export and the appearance of cytoplasmic RNP aggregation. PPQ resistant H1N1 (WSN) viruses were isolated and found to have a NPS377G mutation. Recombinant WSN carrying the S377G NP is resistant to PPQ in anti-influenza and RNA polymerase assays. The WSN virus with the NPS377G mutation also is devoid of the PPQ-mediated RNP nuclear retention and cytoplasmic aggregation. The NPS377G expressing WSN virus is not resistant to the reported NP inhibitors nucleozin. Similarly, the nucleozin resistant WSN viruses are not resistant to PPQ, suggesting that PPQ targets a different site from the nucleozin-binding site. Our results also suggest that NP can be targeted through various binding sites to interrupt the crucial RNP trafficking, resulting in influenza replication inhibition.

CEBPD reverses RB/E2F1-mediated gene repression and participates in HMDB-induced apoptosis of cancer cells.

PURPOSE: Recent evidence indicates that a tumor suppressor gene CEBPD (CCAAT/enhancer-binding protein delta) is downregulated in many cancers including cervical cancer, which provides a therapeutic potential associated with its reactivation. However, little is known for CEBPD activators and the effect of reactivation of CEBPD transcription upon anticancer drug treatment. In this study, we identified a novel CEBPD activator, 1-(2-hydroxy-5-methylphenyl)-3-phenyl-1,3-propanedione (HMDB). The purpose of this study is to characterize the mechanism of HMDB-induced CEBPD activation and its potential effect in cancer therapy. EXPERIMENTAL DESIGN: Methylation-specific PCR assay, reporter assay, and chromatin immunoprecipitation (ChIP) assay were performed to dissect the signaling pathway of HMDB-induced CEBPD transcription. Furthermore, a consequence of HMDB-induced CEBPD expression was linked with E2F1 and retinoblastoma (RB), which discloses the scenario of CEBPD, E2F1, and RB bindings and transcriptional regulation on the promoters of proapoptotic genes, PPARG2 and GADD153. Finally, the anticancer effect of HMDB was examined in xenograft mice. RESULTS: We demonstrate that CEBPD plays an essential role in HMDB-mediated apoptosis of cancer cells. HMDB up-regulates CEBPD transcription through the p38/CREB pathway, thus leading to transcriptional activation of PPARG2 and GADD153. Furthermore, increased level of CEBPD attenuates E2F1-induced cancer cell proliferation and partially rescues RB/E2F1-mediated repression of PPARG2 and GADD153 transcription. Moreover, HMDB treatment attenuates the growth of A431 xenografts in severe combined immunodeficient mice mice. CONCLUSIONS: These results clearly demonstrate that HMDB kills cancer cells through activation of CEBPD pathways and suggest that HMDB can serve as a superior chemotherapeutic agent with limited potential for adverse side effects.

Antioxidant and amine oxidase inhibitory activities of hydroxyurea.

Hydroxyurea (HU, NH(2)CONHOH), or hydroxycarbamide, is a hydroxamic acid derivative used as a drug for anti-neoplasm and sickle-cell disease. In this study, HU was found to have antioxidant activities against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydroxyl radicals and dose-dependent inhibitory activities against monoamine oxidase (MAO)-A, MAO-B, and semicarbazide-sensitive amine oxidase (SSAO) as compared to controls of clorgyline, deprenyl, and semicarbazide respectively. HU showed mixed-type, competitive-type, and competitive-type inhibition, respectively, with respect to substrates of MAO-A, MAO-B, and SSAO with apparent inhibition constants (Ki) of 19.46, 5.38, and 1.84 microM.

Antioxidant, anti-semicarbazide-sensitive amine oxidase, and anti-hypertensive activities of geraniin isolated from Phyllanthus urinaria.

The wrinkle-fruited leaf flower (Phyllanthus urinaria L.) (Euphorbiaceae) is widely used as a traditional folk medicine for inflammatory relief. Geraniin, the hydrolysable tannin, was purified by a series of chromatographic processes from the 70% aqueous acetone extracts of P. urinaria and identified by NMR [1H (500 MHz) and 13C NMR (126 MHz)] spectra and mass spectroscopy. The scavenging activities of geraniin against DPPH radicals (half-inhibition concentration, IC50, were 0.92 and 1.27 microM, respectively, for pH 4.5 and pH 7.9), hydroxyl radicals (IC50 was 0.11 microM by deoxyribose method and 1.44 microM by electron spin resonance method), and superoxide radicals (IC50 were 2.65 microM) were determined in comparison with positive controls. The inhibitory activities against xanthine oxidase (IC50 were 30.49 microM) were measured. Geraniin also showed dose-dependent inhibitory activities against semicarbazide-sensitive amine oxidase (SSAO, IC50 were 6.58 microM) and against angiotensin converting enzyme (ACE, IC50 were 13.22microM). For kinetic property determinations, geraniin showed competitive inhibitions against SSAO (the apparent inhibition constant, Ki, was 0.70microM) and mixed noncompetitive inhibitions against ACE. Spontaneously hypertensive rats (SHR, 10-week age) were orally administered to once (5 mg geraniin/kg SHR), and changes of systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured over 24 h and compared with the positive control of captopril (2 mg/kg SHR). The geraniin showed antihypertensive activity in lowering SBP and DBP and showed a significant difference from the blank (distilled water) at 2, 4, 6, 8, and 24 h. Healthy food products could use geraniin for antioxidant protection and therapeutic effects in the future.

DPPH radical scavenging and semicarbazide-sensitive amine oxidase inhibitory and cytotoxic activities of Taiwanofungus camphoratus (Chang-chih).

Wild, liquid state culture and solid state culture of Taiwanofungus camphoratus (Chang-chih) were sequentially extracted with cold water, methanol, and hot water to get cold water soluble, methanol soluble, and hot water soluble extracts respectively. The extracts from three Chang-chih were used to determine 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, semicarbazide sensitive amine oxidase inhibitory, and cytotoxic activities against B16-F10 and HT-1080 cell lines. It was found that extracted fractions from three Chang-chih exhibited the different levels of biological activities.

Antihypertensive activities of a solid-state culture of Taiwanofungus camphoratus (Chang-chih) in spontaneously hypertensive rats.

Wild and solid-state cultures (SSC) of Taiwanofungus camphoratus (aka Antrodia camphorata and Chang-chih [CC]) were sequentially extracted with cold water, methanol, and hot water to get cold-water-soluble (CWS), methanol-soluble (MS), and hot-water-soluble (HWS) extracts, respectively. Only the MS extract exhibited angiotensin-converting enzyme (ACE) inhibitory activities. The antihypertensive effects of the MS extract (10 mg/kg BW) were measured in spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats. MS extract of the SSC type was able to effectively lower the systolic blood pressure (SBP) and diastolic blood pressure (DBP) of SHR, but not of WKY rats, the results being significantly different from those for distilled water only (the blank). However, wild CC and its MS extract were not as effective as the SSC type in reducing SHR blood pressure and had no effect on WKY rats. SSC-type CC might be developed into a health food with the ability to regulate blood pressure.

Crotonaldehyde formation from decomposition of ICH2CH2OH on powdered TiO2.

Adsorption and reactions of 2-iodoethanol on TiO(2) have been studied by Fourier transform infrared spectroscopy. ICH(2)CH(2)OH possesses two reactive centers of C-I and C-OH. It is found that its decomposition leads to the formation of crotonaldehyde on TiO(2). A reaction sequence of ICH(2)CH(2)OH --> ICH(2)CH(2)O- --> CH(3)CHO --> CH(3)CH=CH-CHO is proposed. Although the decomposition routes of C(2)H(5)OH and C(2)H(5)I, both forming C(2)H(5)O- on TiO(2), suggest that -OCH(2)CH(2)O- may play a role in the crotonaldehyde formation, reaction of HOCH(2)CH(2)OH on TiO(2) shows that this is not the case. Adsorbed H(2)O is formed in the ICH(2)CH(2)OH decomposition on TiO(2); however, it is found that ICH=CH(2), possibly generated by ICH(2)CH(2)OH dehydration, is not important in the crotonaldehyde formation.