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1.
Background
Adenylation of nicotinate mononucleotide to nicotinate adenine dinucleotide is the penultimate step in NAD+ synthesis. In Escherichia coli, the enzyme nicotinate mononucleotide adenylyltransferase is encoded by the nadD gene. We have earlier made an initial characterization in vivo of two mutant enzymes, NadD72 and NadD74. Strains with either mutation have decreased intracellular levels of NAD+, especially for one of the alleles, nadD72. 相似文献2.
Brittany L. Howard Philip E. Thompson David T. Manallack 《Journal of computer-aided molecular design》2011,25(8):753-762
Abstract
The similarity between Plasmodium falciparum phosphodiesterase enzymes (PfPDEs) and their human counterparts have been examined and human PDE9A was found to be a suitable template for the construction of homology models for each of the four PfPDE isoforms. In contrast, the architecture of the active sites of each model was most similar to human PDE1. Molecular docking was able to model cyclic guanosine monophosphate (cGMP) substrate binding in each case but a docking mode supporting cyclic adenosine monophosphate (cAMP) binding could not be found. Anticipating the potential of PfPDE inhibitors as anti-malarial drugs, a range of reported PDE inhibitors including zaprinast and sildenafil were docked into the model of PfPDEα. The results were consistent with their reported biological activities, and the potential of PDE1/9 inhibitor analogues was also supported by docking. 相似文献3.
Vítor Mendes Ana Maranha Pedro Lamosa Milton S da Costa Nuno Empadinhas 《BMC biochemistry》2010,11(1):21
Background
Maltose-1-phosphate was detected in Mycobacterium bovis BCG extracts in the 1960's but a maltose-1-phosphate synthetase (maltokinase, Mak) was only much later purified from Actinoplanes missouriensis, allowing the identification of the mak gene. Recently, this metabolite was proposed to be the intermediate in a pathway linking trehalose with the synthesis of glycogen in M. smegmatis. Although the M. tuberculosis H37Rv mak gene (Rv0127) was considered essential for growth, no mycobacterial Mak has, to date, been characterized. 相似文献4.
Toxoplasma (T.) gondii, the causative agent of toxoplasmosis, is a ubiquitous opportunistic pathogen that infects individuals worldwide, and is
a leading cause of severe congenital neurologic and ocular disease in humans. No vaccine to protect humans is available, and
hypersensitivity and toxicity limit the use of the few available medicines. Therefore, safer and more effective medicines
to treat toxoplasmosis are urgently needed. Using the Hybrid Structure Based (HSB) method, we have previously identified small
molecule inhibitors of P. falciparum that seem to target a novel protein–protein interaction between the Myosin tail interacting protein and myosin light chain.
This pathway has been hypothesized to be involved in invasion of host erythrocytes by the parasite and is broadly conserved
among the apicomplexans. Guided by similar computational drug design approaches, we investigated this series of small molecules
as potential inhibitors of T. gondii. Compound C3-21, identified as the most active inhibitor in this series, exhibited an IC50 value ~500 nM against T. gondii. Among the 16 structural analogs of C3-21 tested thus far, nine additional compounds were identified with IC50 values <10.0 μM. In vitro assays have revealed that C3-21 markedly limits intracellular growth of T. gondii tachyzoites, but has no effect on host cell human foreskin fibroblasts (HFF) at concentrations more than a log greater than
the concentration that inhibits the parasites. 相似文献
5.
Johanna Faist Werner Seebacher Marcel Kaiser Reto Brun Robert Saf Robert Weis 《Monatshefte für Chemie / Chemical Monthly》2009,31(6):1261-1268
Abstract
Aroyl derivatives of 2-aminobicyclo-octanes and 2-azabicyclo-nonanes have been synthesized and tested for their activities against the causative organisms of East African trypanosomiasis and malaria tropica. The acylation induced in general loss of antiprotozoal activity, but a single compound showed good antiplasmodial activity against a multiresistant strain of Plasmodium falciparum. 相似文献6.
Abstract
A classical convergent approach for the synthesis of the anticancer drug imatinib has been substantially improved. Imatinib was assembled by coupling the amine and carboxylic acid precursors by using N,N′-carbonyldiimidazole (CDI) as a condensing agent. Both intermediates have been synthesized by novel efficient methods. 相似文献7.
Setshaba D. Khanye Scott G. Franzblau Philip J. Rosenthal Kelly Chibale 《Journal of organometallic chemistry》2011,696(21):3392-3396
Gold(III) thiosemicarbazone complexes derived from [Au(damp-C1,N)Cl2] (2), where damp = dimeth-ylaminoethylphenyl, have been synthesized. The compounds were characterised using various spectroscopic and analytical techniques, including NMR spectroscopy, mass spectrometry, infrared spectroscopy and elemental analysis. The gold complexes were screened for in vitro antimalarial and antitubercular activity. Although incorporation of the gold(III) centre into thiosemicarbazone scaffolds enhanced their efficacy against the malaria parasite Plasmodium falciparum, this trend was not observed for the antitubercular activity of selected thiosemicarbazones against the Mycobacterium tuberculosis virulent strain H37Rv. 相似文献
8.
María J. Tapia María Monteserín Hugh D. Burrows João S. Seixas de Melo Joan Estelrich 《Photochemistry and photobiology》2013,89(6):1471-1478
We have studied the effect of head group and alkyl chain length on β‐phase formation in poly(9,9‐dioctylfluorene) (PFO) solubilized in phospholipid liposomes. Systems studied have three different alkyl chain lengths (1,2‐dimyristoyl‐sn‐glycero‐3‐phosphatidylcholine [DMPC], 1,2‐didodecanoyl‐sn‐glycero‐3‐phosphatidylcholine [DLPC], 1,2‐dipalmitoyl‐sn‐glycero‐3‐phosphatidylcholine [DPPC]) and head groups (1,2‐dimyristoyl‐sn‐glycero‐3‐phosphate monosodium salt [DMPA], 1,2‐dimyristoyl‐sn‐glycero‐3‐phosphoethanolamine [DMPE] and 1,2‐dimyristoyl‐sn‐glycero‐3‐phospho‐l ‐serine sodium salt [DMPS]). Changes in liposome size upon addition of PFO are followed by dynamic light scattering. All the phospholipids induce the formation of PFO β‐phase, which is followed by the emission intensity and deconvolution of the absorption spectra. Both the head group and alkyl chain length affect the yield of β‐phase. The photophysics of PFO incorporated in liposomes is characterized by stationary and time‐resolved fluorescence, whereas the polymer‐phospholipid interactions have been studied by the effect of the PFO concentration on the phospholipid phase transitions (differential scanning calorimetry [DSC]). 相似文献
9.
Thomas Schmidt Malte Lenders Andrea Hillebrand Nicole van Deenen Oliver Munt Rudolf Reichelt Wolfgang Eisenreich Rainer Fischer Dirk Prüfer Christian Schulze Gronover 《BMC biochemistry》2010,11(1):11
Background
Natural rubber is a biopolymer with exceptional qualities that cannot be completely replaced using synthetic alternatives. Although several key enzymes in the rubber biosynthetic pathway have been isolated, mainly from plants such as Hevea brasiliensis, Ficus spec. and the desert shrub Parthenium argentatum, there have been no in planta functional studies, e.g. by RNA interference, due to the absence of efficient and reproducible protocols for genetic engineering. In contrast, the Russian dandelion Taraxacum koksaghyz, which has long been considered as a potential alternative source of low-cost natural rubber, has a rapid life cycle and can be genetically transformed using a simple and reliable procedure. However, there is very little molecular data available for either the rubber polymer itself or its biosynthesis in T. koksaghyz. 相似文献10.
Siphamandla B. Simelane Monisola I. Ikhile Xavier Y. Mbianda 《Phosphorus, sulfur, and silicon and the related elements》2020,195(7):556-561
AbstractA series of 2-substituted vinylidene-1,1-bisphosphonate esters and their acids were synthesized and tested in vitro for activity against Plasmodium falciparum and Trypanosoma brucei. For each compound, % parasite viability in treated wells was calculated relative to untreated controls for both P. falciparum and T. brucei. Fifty percentage inhibitory concentration (IC50) was also determined for the compounds. Chloroquine and pentamidine were used as positive control drug standards for activity against P. falciparum and T. brucei, respectively. The esters had better antiparasitic activity compared to their corresponding acids. Some of the compounds reduced % parasite viability to as low as 24.3% for P. falciparum and down to 0.602% for T. brucei. Tetraethyl-2-(o-tolyl)-ethene-1,1-bisphosphonate (3b) recorded the best IC50 against T. brucei which was 0.0345?µmol/mL. 相似文献
11.
Abstract
Tris(2-ureidobenzyl)amines bearing three differentially substituted arms have been synthesized. They possess an asymmetric nitrogen atom, the pivotal one, and thus they feature C 1 symmetry. The self-assembly of these C 1-symmetric tris(2-ureidobenzyl)amines may potentially lead to multiple regio- and diastereoisomeric capsules coming from the pairing of the four stereoisomeric monomers with configurations (R, P), (S, P), (R, M) and (S, M). The 1H- and 19F{1H}-NMR spectra confirm the presence of dimeric aggregates, as a mixture of several regio- and diastereoisomeric species. 相似文献12.
Abstract
An effective diastereoselective synthesis of (S)-N,N-diethyl-2-formyl-2-(methoxymethoxy)butanamide and (S)-2-formyl-2-(methoxymethoxy)butanoic acid ethyl ester, which are two key chiral building blocks for the synthesis of 20(S)-camptothecins, has been developed by employing an asymmetric bromolactonization using (R)-proline. The (R) compounds were also synthesized to obtain 20(R)-camptothecin. 相似文献13.
Comparison of sterols and fatty acids in two species of <Emphasis Type="Italic">Ganoderma</Emphasis>
Background
Two species of Ganoderma, G. sinense and G. lucidum, are used as Lingzhi in China. Howerver, the content of triterpenoids and polysaccharides, main actives compounds, are significant different, though the extracts of both G. lucidum and G. sinense have antitumoral proliferation effect. It is suspected that other compounds contribute to their antitumoral activity. Sterols and fatty acids have obvious bioactivity. Therefore, determination and comparison of sterols and fatty acids is helpful to elucidate the active components of Lingzhi. 相似文献14.
Daniel Reker Dr. Michael Seet Max Pillong Dr. Christian P. Koch Dr. Petra Schneider Dr. Matthias C. Witschel Dr. Matthias Rottmann Céline Freymond Prof. Dr. Reto Brun Dr. Bernd Schweizer Dr. Boris Illarionov Prof. Dr. Adelbert Bacher Prof. Dr. Markus Fischer Prof.Dr. François Diederich Prof. Dr. Gisbert Schneider 《Angewandte Chemie (International ed. in English)》2014,53(27):7079-7084
The discovery of pyrrolopyrazines as potent antimalarial agents is presented, with the most effective compounds exhibiting EC50 values in the low nanomolar range against asexual blood stages of Plasmodium falciparum in human red blood cells, and Plasmodium berghei liver schizonts, with negligible HepG2 cytotoxicity. Their potential mode of action is uncovered by predicting macromolecular targets through avant‐garde computer modeling. The consensus prediction method suggested a functional resemblance between ligand binding sites in non‐homologous target proteins, linking the observed parasite elimination to IspD, an enzyme from the non‐mevalonate pathway of isoprenoid biosynthesis, and multi‐kinase inhibition. Further computational analysis suggested essential P. falciparum kinases as likely targets of our lead compound. The results obtained validate our methodology for ligand‐ and structure‐based target prediction, expand the bioinformatics toolbox for proteome mining, and provide unique access to deciphering polypharmacological effects of bioactive chemical agents. 相似文献
15.
Background
Study of ERK activation has thus far relied on biochemical assays that are limited to the use of phospho-specific antibodies and radioactivity in vitro, and analysis of whole cell populations in vivo. As with many systems, fluorescence resonance energy transfer (FRET) can be utilized to make highly sensitive detectors of molecular activity. Here we introduce FRET-based ERK Activity Sensors, which utilize variants of Enhanced Green Fluorescent Protein fused by an ERK-specific peptide linker to detect ERK2 activity. 相似文献16.
Shi-Wen Huang Jin-Sheng Cheng Li Qian Suo-Yi Huang 《Research on Chemical Intermediates》2011,37(1):1-9
Abstract
We present herein a new and efficient method for synthesis of bis-pyrazol pyrimidine derivatives by N-alkylation using a microwave-assisted synthetic process. Two new compounds, N-(4,6-bis(3,5-dimethyl-1H-pyrazol-1-yl)methyl nicotinonitrile and 2,6-bis(3,5-dimethyl-1H-pyrazol-1-yl)-4-methyl nicotinonitrile, were synthesized by the N-alkylation reaction. The novel compounds were characterized by Fourier transform infrared spectrometry, ultraviolet spectroscopy, elemental analysis, and nuclear magnetic resonance spectroscopy, etc. The microwave-assisted procedures have noteworthy advantages in terms of thermal efficiency over those carried out by conventional heating methods. 相似文献17.
Abstract
An efficient and practical asymmetric synthesis of erythro-(1R,2S)-8-O-4′-neolignan myrislignan was achieved by using vanillin and pyrogallic acid as the starting materials. Two key steps are involved: preparation of an enantiopure threo alcohol of predictable stereochemistry by dihydroxylation with AD-mix-β, and inversion of the absolute configuration from the threo to the erythro isomer using a Mitsunobu reaction. The route illustrates a new methodology for the synthesis of erythro-8-O-4′-neolignan. 相似文献18.
Synthesis of pseudo-C-nucleosides from β-formyl-α,β-unsaturated ester bearing a β-furanosidic moiety
Jorge M. Pinheiro M. Isabel Ismael J. Albertino Figueiredo Artur M. S. Silva 《Monatshefte für Chemie / Chemical Monthly》2009,46(6):1237-1244
Abstract
Pseudo-C-nucleosides have potential biological activity, and an efficient synthesis of new pseudo-C-nucleosides has been developed via the reaction of a β-formyl-α,β-unsaturated ester bearing a β-sugar moiety with hydrazines in neutral and acidic conditions. The preparation of the β-formyl-α,β-unsaturated ester was accomplished by oxidation of the secondary hydroxyl group of 3-O-benzyl-1,2-O-isopropylidene-α-d-glucofuranose, followed by elongation of its carbon chain with (ethoxycarbonylmethylene)triphenylphosphorane and oxidation of the hydroxymethyl group. 相似文献19.
Kioumars Aghapoor Hossein Reza Darabi Farshid Mohsenzadeh Yadollah Balavar Hesam Daneshyar 《Transition Metal Chemistry》2010,35(1):49-53
Abstract
Among the various transition metal chlorides, zirconium(IV) chloride was found to be an efficient catalyst for the rapid synthesis of a wide range of 2,3-dialkyl- and 2,3-diaryl-quinoxaline and pyrido[2,3-b]pyrazine derivatives in excellent yields at room temperature. The remarkable features of this catalytic process are the mild reaction conditions, quantitative yields, short reaction times, high conversions, tolerability of various functional groups, clean reaction profiles, and operational simplicity. 相似文献20.
Maher F. El-Zohry Thanaa A. Mohamed Essam M. Hussein 《Monatshefte für Chemie / Chemical Monthly》2009,19(4):265-272