Syntheses of nucleosides with 2′-spirolactam and 2′-spiropyrrolidine moieties as potential inhibitors of hepatitis C virus NS5B polymerase

To discover novel nucleosides as potential antiviral agents, 2′-spirolactam and 2′-spiropyrrolidine-containing nucleoside analogs were envisioned. Efficient synthetic routes were developed with an epoxide opening as the key step to establish the quaternary center at the 2′ position, leading to the design and synthesis of uridine analogs 8 and 21, prodrugs 13–16, and cytidine analog 11.     

Two novel abietane dimers from transformed root cultures of Salvia broussonetii

Broussonetone A (1) and broussonetone B (2), two novel dimeric abietane diterpenes, have been isolated from Salvia broussonetii root cultures transformed by Agrobacterium rhizogenes. The structure of broussonetone A was determined from spectroscopic data and confirmed by X-ray analysis. This dimer can be formed by a [4+2]-cycloaddition of two molecules of 13β-hydroxyabieta-8(14),9(11)-dien-12-one. NMR data of broussonetone B indicated that the C-20 methyl in part B of the broussonetone A molecule had been substituted by an aldehyde group. Thus, broussonetone B could be formed by an analogous Diels Alder reaction between 13β-hydroxyabieta-8(14),9(11)-dien-12-one as the dienophile and its 20-oxo derivative as the electrophile.     

Optimised synthesis of diamino-triazinylmethyl benzoates as inhibitors of Rad6B ubiquitin conjugating enzyme

Recently, we have identified the first inhibitors of Rad6B, an E2 enzyme essential for post-replication DNA repair and a potential new drug target for the treatment of breast cancer. We report two newly optimised synthetic routes to our [4-amino-6-(phenylamino)-1,3,5-triazin-2-yl]methyl 4-nitrobenzoate target compounds TZ8 and TZ9 with general applicability for further structure–activity relationship studies around this pharmacophore. The key step involved the condensation/cyclisation between phenylbiguanide and either ethyl bromoacetate or dimethyloxalate in good yield.     

Syntheses of 4′-spirocyclic phosphono-nucleosides as potential inhibitors of hepatitis C virus NS5B polymerase

To discover novel nucleosides as potential antiviral agents, 4′-spirocyclic phosphono-nucleosides were designed to mimic the monophosphate of R-1479, a known nucleoside inhibitor of HCV NS5B. Bypassing the first kinase step to nucleoside monophosphate is viewed as advantageous since this phosphorylation is often observed as the rate-limiting transformation to the active NTP for many nucleosides. Efficient synthetic routes were developed with a triphenylphosphine–iodine cyclization reaction as the key step to form the tetrahydrofuran 4′-spirocycle. The desired 4′-spirocyclic phosphono-cytidine analogs 12a, 12b, and 16 were prepared in 11 steps.     

利用无标记的分子信标及核酸染料SYBR Green Ⅰ检测乙肝病毒

本文以野生型的乙型肝炎病毒(HBV)核酸片段为研究对象,利用无标记的分子信标及核酸染料SYBR Green I,建立了一种高灵敏、高选择性的特定序列核酸检测方法.在优化条件下,目标DNA浓度为4×10-11~400×10-11 mol/L之间时,SYBR Green I的荧光强度(ΔI)与目标DNA的浓度(C)具有良好的线性关系,其拟合的回归方程为ΔI=1.9556 C+31.4659(R2=0.9956),方法检测限(3ζ)为2×10-11 mol/L.该方法操作简单、检测速度快、灵敏度高、重现性好、检出限低.利用该方法,结合不对称PCR技术,实现了对HBV的定量检测.     

一例水溶液中识别铜离子的染料探针

通过罗丹明B与乙二胺反应生成的中间体合成了一例可以对铜离子进行比色检测的探针R-Cu.R-Cu可以实现对在HEPES(5 mmol/L;pH 7.4)溶液中Cu2+的比色可视化识别,加入Cu2+后,R-Cu的吸收明显增强,呈现出罗丹明B的紫红色.探针对Cu2+具有较高的选择性和灵敏性,对其他常见的金属离子具有较强的抗干扰能力.该探针可以在较宽的特别是近中性pH环境下有效检测Cu2+,最低检出限为2.70×10?7 mol/L.     

Voltammetric Determination of Aflatoxin B1

For the first time the possibility of voltammetry used for the determination of aflatoxin B1 on a glassy carbon electrode was shown. The effect of pH of a supporting electrolyte on the analytical signal of aflatoxin B1 has been investigated and it was shown that there is a more pronounced peak with a maximum current at pH of 5.33. The most favorable supporting electrolyte for a linear range of detectable concentrations of aflatoxin B1 – 0.1 M (NH₄)₂SO₄ was determined. The results of research on the development of conditions of voltammetric measurement of aflatoxin B1 are presented.     

Two novel heterobimetallic metal-organic frameworks for the enhanced catalytic thermolysis and laser ignition of CL-20

The study of multiple complex catalytic mechanisms is currently one of the great scientific issues for the application of high-energy solid propellants. Two novel heterobimetallic metal-organic frameworks (MOFs), Ba₄Pb₄(CH₃CO₂)₈ [(CH₆CO₂)₄Pb](CH₃CO₂)₄ (PbBa-MOF) and Ba₂Ni(CO₂H)₆(OH₂)₄ (NiBa-MOF), were prepared via the solvothermal method, and their structures and composition were characterized by X-ray diffraction (XRD), scanning electron microscope (SEM), X-ray photoelectron spectroscopy (XPS), fourier transform infrared spectroscopy (FTIR) techniques and N₂ adsorption/desorption experiment. The thermal decomposition characteristics of the two MOFs and their catalytic performances on the hexanitro hexaazaisowurtzitane (CL-20) thermolysis were also studied by differential scanning calorimetr (DSC) and thermogravimetric-fourier transform infrared spectroscopy-mass spectrum (TG-FTIR-MS) methods. The results showed that the NiBa-MOF presented a lower initial decomposition temperature than the PbBa-MOF, and the difference of the MOFs structures affected the starting point of thermal decomposition. Compared with the pure CL-20, the thermolysis peak temperature and apparent activation energy (E_a) of the CL-20/PbBa-MOF mixture were decreased by 2.2 °C and 23.76 kJ?mol^?1, respectively. The E_a of CL-20/NiBa-MOF mixture was lower and 42.01 kJ?mol^?1, indicating the better catalytic activity of NiBa-MOF. The thermolysis catalytic mechanisms were studied by analyzing the transformation of gas products during the pyrolysis of mixtures. The effect of these two MOFs on the CL-20 thermolysis is primarily owing to the strong attraction of metal cations to electronics, bimetallic synergistic catalysis, and the release of active free radicals. Furthermore, the laser ignition and flame propagation features showed that these two MOFs reduced the minimum ignition power density and ignition delay time of the CL-20, and the flame becomes brighter and more luminous. The influence of the two MOFs on the flame bright spot of CL-20 based mixtures was described.     

In Vitro Anticancer Activity of Nanoformulated Mono- and Di-nuclear Pt Compounds

Nanoformulations of mononuclear Pt complexes cis-PtCl₂(PPh₃)₂ ( 1 ), [Pt(PPh₃)₂(L−Cys)] ⋅ H₂O ( 3 , L−Cys=L-cysteinate), trans-PtCl₂(PPh₂PhNMe₂)₂ ( 4 ; PPh₂PhNMe₂=4-(dimethylamine)triphenylphosphine), trans-PtI₂(PPh₂PhNMe₂)₂ ( 5 ) and dinuclear Pt cluster Pt₂(μ-S)₂(PPh₃)₄ ( 2 ) have comparable cytotoxicity to cisplatin against murine melanoma cell line B16F10. Masking of these discrete molecular entities within the hydrophobic core of Pluronic® F-127 significantly boosted their solubility and stability, ensuring efficient cellular uptake, giving in vitro IC₅₀ values in the range of 0.87–11.23 μM. These results highlight the potential therapeutic value of Pt complexes featuring stable Pt−P bonds in nanocomposite formulations with biocompatible amphiphilic polymers.     

Anti-atherosclerotic activity of Betulinic acid loaded polyvinyl alcohol/methylacrylate grafted Lignin polymer in high fat diet induced atherosclerosis model rats

Betulinic acid is one such natural pentacyclic triterpenoid compound, holding various pharmacological properties but its poor bioavailability is the only limitation. One of the biological macromolecules such as Lignin is a plant-derived aromatic, eco-friendly and low-cost polymer that certainly self-assembles into nano-sized colloids. Therefore, onto the current investigation, we increased the bioavailability of betulinic acid by coating on to a nanopolymer prepared with poly vinyl alcohol, lignins and methyl acrylate. Betulinic acid loaded polyvinyl alcohol/ethylacrylate grafted Lignin polymer (PVA/Lig-g-MA) nanoformulation was characterized using FTIR, XRD, SEM and TEM analysis and also the drug entrapment, in vitro drug releasing capacity was done to examine the efficiency of the nanoformulation of a drug. The MTT assay was evaluated the cytotoxicity of synthesized nanoformulation against normal endothelial cells HUVEC and HAPEC to confirm the side effects of the drug. The anti-atherosclerotic property of the nanoformulation was ascertained in both in vitro condition (with HUVEC and HPAEC) and in vivo studies (with Wistar rats). As a result, the characterization studies and in vitro studies clearly confirmed the Betulinic acid loaded PVA/Lig-g-MA nanoformulation is an ideal nanopolymer and it doesn’t cause any cytotoxic effect in normal endothelial cells. It also decreased the lipopolysaccharides induced inflammation through the down-regulation of NFκB and MAP/JNK signaling molecule expressions. Following in vivo results confirmed the synthesized nanoformulation effectively decreased the hyperchlostremia, inflammation and vasoconstriction, which induced over high fat diet. The results of histopathological analysis of cardiac tissues also confirmed the cardioprotective role of synthesized nanoformulation. Overall, both the in vitro and in vivo studies authentically proven the Betulinic acid loaded PVA/Lig-g-MA nanoformulation would be a potent cost effective anti-atherosclerotic nanodrug.