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31.
Daniel C. Capaldi Alessandra Eleuteri Qin Chen Raymond F. Schinazi 《Nucleosides, nucleotides & nucleic acids》2013,32(4):403-416
Abstract The synthesis of pyrimidine nucleosides, cis-N-1-[(2-hydroxymethyl)-1,3-dioxan-5-yl]uracil (4) cis-N-1-[(2-hydroxymethyl)-1,3-dioxan-5-yl]thymine (5) and cis-N-1-[(2-hydroxymethyl)-1,3-dioxan-5-yl]cytosine (6) and their corresponding trans isomers is described. Compound 4 showed modest, selective activity against human immunodeficiency virus in acutely infected primary human lymphocytes. 相似文献
32.
Chang Hyun Oh Lian Jin Liu Joon Hee Hong 《Nucleosides, nucleotides & nucleic acids》2013,32(10):721-733
A novel 3′,4′-dimethyl-5′-norcarbocyclic adenosine phosphonic acid was prepared using acyclic stereoselective route from 4-hydroxybutan-2-one (4). To improve the cellular permeability and enhance the anti-HIV activity of this phosphonic acid, a (bis)SATE phosphonodiester nucleoside prodrug (20) was prepared and its chemical stability was evaluated. The newly synthesized bis(SATE) analogue (20) and its parent nucleoside phosphonic acid (18) were assayed for anti-HIV activity using an in vitro assay system in a CEM cell line. 相似文献
33.
Etsuko Kawashima Yasuhiro Nakanishi Yusuke Terui Hideyuki Tomitori Keiko Kashiwagi Yusuke Ohba 《Nucleosides, nucleotides & nucleic acids》2013,32(4):196-205
Pyrrole polyamide-2′-deoxyguanosine 5′-phosphate hybrid (Hybrid 4) was synthesized and evaluated in terms of the inhibition of mouse mammary carcinoma FM3A cell growth. Hybrid 4 was found to exhibit dose-dependent inhibition of cell growth. 相似文献
34.
The discovery of threosyl phosphonate nucleoside (PMDTA, EC50 = 2.53 μM) as a potent anti-HIV agent has led to the synthesis and biological evaluation of 5 ′-deoxyversions of threosyl phosphonate nucleosides from 1,4-dihydroxy-2-butene. The synthesized nucleoside phosphonic acid analogues 14 and 19 were tested for anti-HIV activity as well as cytotoxicity. The adenine analogue 14 exhibits moderate in vitro anti-HIV-1 activity (EC50 = 12.6 μM). 相似文献
35.
On the basis of the discovery that the threosyl nucleoside phosphonate PMDTA is a potent anti-HIV compound, we synthesized several 4′-trifluoromethyl-5′-deoxyapiosyl nucleoside phosphonic acids and evaluated their anti-HIV activity. An efficient synthetic route was optimized, starting from an α-trifluoromethyl-α,β-unsaturated ester. Glycosylation of the purine nucleosidic bases with a glycosyl donor yielded modified nucleoside intermediates, which were then phosphonated and hydrolyzed to provide the targeted nucleoside analogs. Once synthesized, the anti-HIV and cytotoxic activities of each analog were evaluated. None of the analogs showed significant anti-HIV activity at concentrations up to 100 μM. 相似文献
36.
Yuan Yuan Zhang Jun Hong Liu Yuan ming Zhou Yu Yan Zhang Ying Liu Ting Yun Gong Jing Wang 《Process Biochemistry》2013,48(8):1119-1125
A new two-phase kinetic model of sporulation of Clonostachys rosea in a new solid-state fermentation (SSF) reactor was proposed. The model including exponential and logistic models was applied to study the simultaneous effect of temperature, initial moisture content, medium thickness and surface porosity of the plastic membrane on C. rosea sporulation. The model fits experimental data very well and allows accurate predictions of spore production. The maximum spore production achieved 3.360 × 1010 (spores/gDM), about 10 times greater than that in traditional SSF reactor(data not shown). The new reactor can provide two times sporulation surface area. Moisture content can be adjusted by changing the surface porosity to meet the spore production. Two mixings carried out during fermentation makes medium loose and results in a mass of new sporulation surface area. Therefore, the new SSF reactor would have great potential for application in bulk spore production of fungal biocontrol agents. 相似文献
37.
目的:设计并合成抗肿瘤药物帕玛度胺的3位N取代的新型类似物。方法:从3-硝基邻苯二甲酸(2)和N-(叔丁氧羰基).L-谷氨酰胺(4)出发,经过六步反应得到目标化合物。3-硝基邻苯二甲酸(2)经脱水制得3-硝基邻苯二甲酸酐(3)。用N-(叔丁氧羰基)-L-谷氨酰胺(4)经闭环、脱保护制得3-氨基-2,6-哌啶二酮三氟乙酸盐(6)。4与6经缩合、钯碳催化氢化制得免疫调节剂Pomalidomide(8),(8)经过酰化得到3-乙酰氨基-N-(2,6-二氧代-3-哌啶基)邻苯二甲酰亚胺(1)。以(4)计总收率约34.9%。结果:得到3-乙酰氨基-N-(2,6-二氧代-3-哌啶基)-邻苯二甲酰亚胺(1),应用于细胞活性测试。结论:改进了帕玛度胺的合成工艺,得到了3位N乙酰化的新型帕玛度胺类似物(1),初步研究显示(1)的生物活性与帕玛度胺接近。 相似文献
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The increasing incidence of hospital acquired infections caused by antibiotic resistant pathogens has led to an increase in morbidity and mortality, finding alternative antibiotics unaffected by resistance mechanisms is fundamentally important for treating this problem. Naturally occurring proteins usually carry short peptide fragments that exhibit noticeable biological activity against a wide variety of microorganisms such as bacteria, fungi and protozoa. Traditional discovery of such antimicrobially active fragments (i.e. antimicrobial peptides, AMPs) from protein repertoire is either random or led by chance. Here, we report the use of a rational protocol that combines in silico prediction and in vitro assay to identify potential AMPs with high activity and low toxicity from the entire human genome. In the procedure, a three-step inference strategy is first proposed to perform genome-wide analysis to infer AMPs in a high-throughput manner. By employing this strategy we are able to screen more than one million peptide candidates generated from various human proteins, from which we identify four highly promising samples, and subsequently their antibacterial activity on five strains as well as cytotoxicity on human myoblasts are tested experimentally. As a consequence, two high-activity, low-toxicity peptides are discovered, which could be used as the structural basis to further develop new antibiotics. In addition, from 1491 known AMPs we also derive a quantitative measure called antibacterial propensity index (API) for 20 naturally occurring amino acids, which shows a significant allometric correlation with the theoretical minimal inhibitory concentration of putative peptides against Gram-positive and Gram-negative bacteria. This study may provide a proof-of-concept paradigm for the genome-wide discovery of novel antimicrobial peptides by using a combination of in silico and in vitro analyses. 相似文献