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排序方式: 共有119条查询结果,搜索用时 8 毫秒
21.
Liu C Lin J Pitt S Zhang RF Sack JS Kiefer SE Kish K Doweyko AM Zhang H Marathe PH Trzaskos J Mckinnon M Dodd JH Barrish JC Schieven GL Leftheris K 《Bioorganic & medicinal chemistry letters》2008,18(6):1874-1879
Rational design, synthesis, and SAR studies of a novel class of benzothiazole based inhibitors of p38alpha MAP kinase are described. The issue of metabolic instability associated with vicinal phenyl, benzo[d]thiazol-6-yl oxazoles/imidazoles was addressed by the replacement of the central oxazole or imidazole ring with an aminopyrazole system. The proposed binding mode of this new class of p38alpha inhibitors was confirmed by X-ray crystallographic studies of a representative inhibitor (6a) bound to the p38alpha enzyme. 相似文献
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Mittal A. Darji Rahul M. Lalge Sushrut P. Marathe Tarul D. Mulay Tasnim Fatima Alia Alshammari Hyung Kyung Lee Michael A Repka S. Narasimha Murthy 《AAPS PharmSciTech》2018,19(1):12-26
The choice of excipients constitutes a major part of preformulation and formulation studies during the preparation of pharmaceutical dosage forms. The physical, mechanical, and chemical properties of excipients affect various formulation parameters, such as disintegration, dissolution, and shelf life, and significantly influence the final product. Therefore, several studies have been performed to evaluate the effect of drug-excipient interactions on the overall formulation. This article reviews the information available on the physical and chemical instabilities of excipients and their incompatibilities with the active pharmaceutical ingredient in solid oral dosage forms, during various drug-manufacturing processes. The impact of these interactions on the drug formulation process has been discussed in detail. Examples of various excipients used in solid oral dosage forms have been included to elaborate on different drug-excipient interactions. 相似文献
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Inflammatory platelet-activating factor-like phospholipids in oxidized low density lipoproteins are fragmented alkyl phosphatidylcholines. 总被引:4,自引:0,他引:4
G K Marathe S S Davies K A Harrison A R Silva R C Murphy H Castro-Faria-Neto S M Prescott G A Zimmerman T M McIntyre 《The Journal of biological chemistry》1999,274(40):28395-28404
Oxidation of human low density lipoprotein (LDL) generates proinflammatory mediators and underlies early events in atherogenesis. We identified mediators in oxidized LDL that induced an inflammatory reaction in vivo, and activated polymorphonuclear leukocytes and cells ectopically expressing human platelet-activating factor (PAF) receptors. Oxidation of a synthetic phosphatidylcholine showed that an sn-1 ether bond confers an 800-fold increase in potency. This suggests that rare ether-linked phospholipids in LDL are the likely source of PAF-like activity in oxidized LDL. Accordingly, treatment of oxidized LDL with phospholipase A(1) greatly reduced phospholipid mass, but did not decrease its PAF-like activity. Tandem mass spectrometry identified traces of PAF, and more abundant levels of 1-O-hexadecyl-2-(butanoyl or butenoyl)-sn-glycero-3-phosphocholines (C(4)-PAF analogs) in oxidized LDL that comigrated with PAF-like activity. Synthesis showed that either C(4)-PAF was just 10-fold less potent than PAF as a PAF receptor ligand and agonist. Quantitation by gas chromatography-mass spectrometry of pentafluorobenzoyl derivatives shows the C(4)-PAF analogs were 100-fold more abundant in oxidized LDL than PAF. Oxidation of synthetic alkyl arachidonoyl phosphatidylcholine generated these C(4)-PAFs in abundance. These results show that quite minor constituents of the LDL phosphatidylcholine pool are the exclusive precursors for PAF-like bioactivity in oxidized LDL. 相似文献
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Hari?Om?SinghEmail author Shruti?D?Marathe Sumitra?Nain Dharmesh?Samani Vijay?Nema Manisha?V?Ghate R?R?Gangakhedkar 《Journal of biosciences》2017,42(3):481-490
The pathogenesis of HIV-associated neurocognitive disorder (HAND) is modulated by host genetic susceptibility factors such as Matrix metalloproteinases (MMPs). Promoter polymorphism of MMP-1 and MMP-3 may modify the expression of the gene. Hence, we evaluated the association of MMP-1-16072G/1G and MMP-3-1612 5A/6A polymorphisms with development of HAND and the modulation of pathogenesis of HAND. We enrolled a total of 180 individuals, 50 HIV-infected individuals with HAND, 130 without HAND, and 150 healthy controls. Polymorphism of MMP-1 and MMP-3 were genotyped by PCR-RFLP. MMP-1-1607 2G1G, -16071G/2G-1G/1G genotypes and -1607 1G allele were associated with the development of HAND (OR = 1.64, P = 0.05; OR = 1.45, P = 0.04; OR = 1.69, P = 0.05). MMP-1-16071G1G, MMP-3-16125A5A genotypes increased the risk for the development of HAND (OR = 1.78, P = 0.25; OR = 2.39, P = 0.13). MMP-3-1612 5A5A, -1612 6A/5A-5A/5A genotypes and -1612 5A allele were associated with the reduced risk of HAND (OR = 0.40, P = 0.05; OR = 0.53, P = 0.04; OR = 0.40, P = 0.01). Haplotype 5A1G increased the risk of development of HAND (OR = 1.93, P = 0.05). As observed in advanced HIV disease stage, MMP-1-1607 1G1G genotype enhance the risk for advancement of HIV disease (OR = 1.69, P = 0.89). MMP-3-1612 6A5A genotype showed higher risk for development of HAND in alcohol users (0R = 1.65, P = 0.44). MMP-1 genotype may have an influence on development of HAND whereas MMP3-1612 5A5A genotype may reduce risk for pathogenesis of HAND. 相似文献
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Ila A Marathe Stella M Lai Walter J Zahurancik Michael G Poirier Vicki
H Wysocki Venkat Gopalan 《Nucleic acids research》2021,49(16):9444
The ribonucleoprotein (RNP) form of archaeal RNase P comprises one catalytic RNA and five protein cofactors. To catalyze Mg2+-dependent cleavage of the 5′ leader from pre-tRNAs, the catalytic (C) and specificity (S) domains of the RNase P RNA (RPR) cooperate to recognize different parts of the pre-tRNA. While ∼250–500 mM Mg2+ renders the archaeal RPR active without RNase P proteins (RPPs), addition of all RPPs lowers the Mg2+ requirement to ∼10–20 mM and improves the rate and fidelity of cleavage. To understand the Mg2+- and RPP-dependent structural changes that increase activity, we used pre-tRNA cleavage and ensemble FRET assays to characterize inter-domain interactions in Pyrococcus furiosus (Pfu) RPR, either alone or with RPPs ± pre-tRNA. Following splint ligation to doubly label the RPR (Cy3-RPRC domain and Cy5-RPRS domain), we used native mass spectrometry to verify the final product. We found that FRET correlates closely with activity, the Pfu RPR and RNase P holoenzyme (RPR + 5 RPPs) traverse different Mg2+-dependent paths to converge on similar functional states, and binding of the pre-tRNA by the holoenzyme influences Mg2+ cooperativity. Our findings highlight how Mg2+ and proteins in multi-subunit RNPs together favor RNA conformations in a dynamic ensemble for functional gains. 相似文献
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Sandeep A. Walujkar Shreyas V. Kumbhare Nachiket P. Marathe Dhrati V. Patangia Parimal S. Lawate Renu S. Bharadwaj Yogesh S. Shouche 《World journal of microbiology & biotechnology》2018,34(6):76
Dysbiosis of intestinal microflora has been postulated in ulcerative colitis (UC), which is characterized by imbalance of mucosal tissue associated bacterial communities. However, the specific changes in mucosal microflora during different stages of UC are still unknown. The aim of the current study was to investigate the changes in mucosal tissue associated microbiota during acute exacerbations and remission stages of UC. The mucosal microbiota associated with colon biopsy of 12 patients suffering from UC (exacerbated stage) and the follow-up samples from the same patients (remission stage) as well as non-IBD subjects was studied using 16S rRNA gene-based sequencing and quantitative PCR. The total bacterial count in patients suffering from exacerbated phase of UC was observed to be two fold lower compared to that of the non-IBD subjects (p?=?0.0049, Wilcox on matched-pairs signed rank tests). Bacterial genera including Stenotrophomonas, Parabacteroides, Elizabethkingia, Pseudomonas, Micrococcus, Ochrobactrum and Achromobacter were significantly higher in abundance during exacerbated phase of UC as compared to remission phase. The alterations in bacterial diversity with an increase in the abnormal microbial communities signify the extent of dysbiosis in mucosal microbiota in patients suffering from UC. Our study helps in identifying the specific genera dominating the microbiota during the disease and thus lays a basis for further investigation of the possible role of these bacteria in pathogenesis of UC. 相似文献