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1.
Singh SB Ball RG Bills GF Cascales C Gibbs JB Goetz MA Hoogsteen K Jenkins RG Liesch JM Lingham RB Silverman KC Zink DL 《The Journal of organic chemistry》1996,61(22):7727-7737
Farnesyl-protein transferase (FPTase) is an enzyme responsible for the farnesylation of Ras protein. Farnesylation is required for cell-transforming activity in several tumor-types, and therefore, inhibition of FPTase activity may be a potential target for anticancer drugs. Our continued search for novel inhibitors led to the isolation of a number of bicyclic resorcinaldehyde cyclohexanone derivatives named here cylindrols A(1) to A(4), cylindrols B and B(1), and a number of known compounds, from Cylindrocarpon lucidum. The compounds were isolated by bioassay-guided separation using Sephadex LH-20, silica gel, and reverse phase HPLC. Structures were elucidated by extensive application of 2D NMR and X-ray crystallography. The determination of absolute stereochemistry was accomplished by CD measurements. Chemical transformations of the most abundant compound resulted in a number of key derivatives which were critical for the evaluation of structure activity relationship. These compounds are members of ascochlorin family and showed a wide range of inhibitory activity (0.7 &mgr;M to >140 &mgr;M) against FPTase. The FPTase activity was noncompetitive with respect to both substrates. Isolation, structures, chemical transformations, and FPTase activity are discussed in detail. 相似文献
2.
Benjamin Large Natalia G. Baranska Rosalind L. Booth Keith S. Wilson Anne-Kathrin Duhme-Klair 《Current Opinion in Green and Sustainable Chemistry》2021
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3.
Harry R. Hudson Rosalind J. Lee Ray W. Matthews 《Phosphorus, sulfur, and silicon and the related elements》2013,188(9):1691-1709
n-Benzhydryl-protected diethyl[3.3pc] esters of 1-amino-1-aryl- (phenyl, cumyl, p-dimethylaminophenyl, piperonyl, 1′-naphthyl, 9′-anthryl, 1′-pyrenyl) and 1-amino-1-heteroaryl- (furyl, 2′-thienyl, 3′-thienyl, 2′-pyrrolyl)-methanephosphonic acids, prepared by the addition of diethyl phosphite to the corresponding benzhydryl imines, have been isolated, purified, and characterized. The presence of chiral α -carbon and prochiral phosphorus in these esters gives rise to complicated features in their NMR spectra, which are discussed. Hydrolysis of the crude 1-aryl compounds in situ gave modest yields of the corresponding aminophosphonic acids (except for 1′-pyrenyl). Of the 1-heteroaryl derivatives, only the 2′-thienyl compound gave the expected aminophosphonic acid; in other cases, alternative[-18pc] modes of decomposition may occur under hydrolytic conditions. NMR and mass spectral data are given for all products. 相似文献
4.
Prof. Christopher Batchelor-McAuley Dr. Minjun Yang Prof. Rosalind E. M. Rickaby Prof. Richard G. Compton 《Chemistry (Weinheim an der Bergstrasse, Germany)》2022,28(68):e202202290
The ultimate fate, over the course of millennia, of nearly all of the carbon dioxide formed by humankind is for it to react with calcium carbonate in the world's oceans. Although, this reaction is of global relevance, aspects of the calcite dissolution reaction remain poorly described with apparent contradictions present throughout the expansive literature. In this perspective we aim to evidence how a lack of appreciation of the role of mass-transport may have hampered developments in this area. These insights have important implications for both idealised experiments performed under laboratory conditions and for the measurement and modelling of oceanic calcite sediment dissolution. 相似文献
5.
Harry R. Hudson Rosalind J. Lee 《Phosphorus, sulfur, and silicon and the related elements》2014,189(7-8):1149-1155
AbstractReports on the anticancer activity of representative α-aminophosphonic acid derivatives are briefly reviewed, with comments where possible on modes of action. Preliminary in vitro screening results are also presented for selected dialkyl α-aryl (or heteroaryl)-α-(diphenylmethylamino)methanephosphonates against the National Cancer Institute (NCI) 60-cell line panel of human tumor cells, which showed average response parameters for active compounds of GI50 between 4.81 × 10?6 and 2.40 × 10?5 M, TGI between 1.88 and 6.28 × 10?5 M, and LC50 between 5.71 and 9.37 × 10?5 M. The highest activity was shown by the α-phenyl compound for which GI50 10?7 M was recorded against leukemia cell line MOLT-4. 相似文献
6.
Rosalind Wolstenholme Robert Bradshaw Malcolm R. Clench Simona Francese 《Rapid communications in mass spectrometry : RCM》2009,23(19):3031-3039
Identification of suspects via fingermark analysis is one of the mainstays of forensic science. The success in matching fingermarks, using conventional fingermark scanning and database searching, strongly relies on the enhancement method adopted for fingermark recovery; this in turn depends on the components present in the fingermarks, which will change over time. This work aims to develop a robust methodology for improved analytical detection of the fingermark components. For the first time, matrix‐assisted laser desorption/ionisation mass spectrometry imaging (MALDI‐MSI) has been used to image endogenous lipids from fresh and aged, groomed and ungroomed fingermarks. The methodology was initially developed using oleic acid which was detected along with its degradation products over a 7‐day period, at three different temperatures in a time‐course experiment. The optimised methodology was then transferred to the imaging analysis of real fingermark samples. Fingermark patterns were reconstructed by retrieving the m/z values of oleic acid and its degradation products. This allowed the three aged fingermarks to be distinguished. In order to prove that MALDI‐MSI can be used in a non‐destructive way, a simple washing protocol was adopted which returned a fingermark that could be further investigated with classical forensic approaches. The work reported here proves the potential and the feasibility of MALDI‐MSI for the forensic analysis of fingermarks, thus making it competitive with other MSI techniques such as desorption electrospray ionisation (DESI)‐MS. The feasibility of using MALDI‐MSI in fingermark ageing studies is also demonstrated along with the potential to be integrated into routine fingermark forensic analysis. Copyright © 2009 John Wiley & Sons, Ltd. 相似文献
7.
A GC-high-resolution isotope dilution MS (IDMS) method for the quantification of melamine in milk powder is described. The developed technique is compared to the LC-IDMS/MS technique, typically used for the determination of melamine in various matrices. The accuracy of the GC-high-resolution IDMS method was demonstrated when a small degree of equivalence was obtained in a regional comparative study involving the determination of melamine in milk powder. 相似文献
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10.
Leesa S Ferguson Stuart Creasey Rosalind Wolstenholme Malcolm R Clench Simona Francese 《Journal of mass spectrometry : JMS》2013,48(6):677-684
Matrix‐assisted laser desorption/ionisation mass spectrometry imaging (MALDI‐MSI) has proven to be a powerful analytical tool to investigate problems in several fields of life science. A novel application is in the field of forensics, particularly in the analysis of latent fingermarks. This technology enables images of the fingermark ridge detail and additional intelligence to be simultaneously obtained. Although several methods are available to deposit the MALDI matrix, to make the technology forensically operational, another deposition approach was devised and reported, namely the ‘dry–wet’ method. In the present study, the efficiency of the dry–wet method was evaluated and compared with the conventional spray coat methodology. Results indicate that the dry–wet method is superior for all the donors' typologies in terms of ion signal intensity and clarity of the ridge details. To underpin the reasons of this efficiency, scanning electron microscopy analyses were carried out in parallel to MALDI‐MSI experiments using matrices of different particle size. Results have confirmed that the particle size plays an important role in the efficiency of the method as higher quality images and higher intensity spectra are produced as the matrix particle size decreases. Copyright © 2013 John Wiley & Sons, Ltd. 相似文献