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991.
Shikha S. Chauhan Leena Gupta Monika Mittal Preeti Vishwakarma Suman Gupta Prem M.S. Chauhan 《Bioorganic & medicinal chemistry letters》2010,20(21):6191-6194
A series of indolylglyoxylamide derivatives have been synthesized and evaluated in vitro against amastigote form of Leishmania donovani. Compound 8c has been identified as the most active analog of the series with IC50 value of 5.17 μM and SI value of 31.48, and is several folds more potent than the standard drugs sodium stilbogluconate and pentamidine. 相似文献
992.
Stevan Pecic Pooja Makkar Sandeep Chaudhary Boojala V. Reddy Hernan A. Navarro Wayne W. Harding 《Bioorganic & medicinal chemistry》2010,18(15):5562-5575
Analogs of nantenine were docked into a modeled structure of the human 5-HT2A receptor using ICM Pro, GLIDE, and GOLD docking methods. The resultant docking scores were used to correlate with observed in vitro apparent affinity (Ke) data. The GOLD docking algorithm when used with a homology model of 5-HT2A, based on a bovine rhodopsin template and built by the program MODELLER, gives results which are most in agreement with the in vitro results. Further analysis of the docking poses among members of a C1 alkyl series of nantenine analogs, indicate that they bind to the receptor in a similar orientation, but differently than nantenine. Besides an important interaction between the protonated nitrogen of the C1 alkyl analogs and residue Asp155, we identified Ser242, Phe234, and Gly238 as key residues responsible for the affinity of these compounds for the 5-HT2A receptor. Specifically, the ability of some of these analogs to establish a H-bond with Ser242 and hydrophobic interactions with Phe234 and Gly238 appears to explain their enhanced affinity as compared to nantenine. 相似文献
993.
Purine nucleoside phosphorylase (PNP) is an important component of the nucleotide salvage pathway in apicomplexan parasites and a potential target for drug development. The intracellular pathogen Toxoplasma gondii was therefore tested for sensitivity to immucillins, transition state analogs that exhibit high potency against PNP in the malaria parasite Plasmodium falciparum. Growth of wild-type T. gondii is unaffected by up to 10 microm immucillin-H (ImmH), but mutants lacking the (redundant) purine salvage pathway enzyme adenosine kinase are susceptible to the drug, with an IC50 of 23 nm. This effect is rescued by the reaction product hypoxanthine, but not the substrate inosine, indicating that ImmH acts via inhibition of T. gondii PNP. The primary amino acid sequence of TgPNP is >40% identical to PfPNP, and recombinant enzymes exhibit similar kinetic parameters for most substrates. Unlike the Plasmodium enzyme, however, TgPNP cannot utilize 5'-methylthio-inosine (MTI). Moreover, TgPNP is insensitive to methylthio-immucillin-H (MT-ImmH), which inhibits PfPNP with a Ki* of 2.7 nm. MTI arises through the deamination of methylthio-adenosine, a product of the polyamine biosynthetic pathway, and its further metabolism to hypoxanthine involves PfPNP in purine recycling (in addition to salvage). Remarkably, analysis of the recently completed T. gondii genome indicates that polyamine biosynthetic machinery is completely lacking in this species, obviating the need for TgPNP to metabolize MTI. Differences in purine and polyamine metabolic pathways among members of the phylum Apicomplexa and these parasites and their human hosts are likely to influence drug target selection strategies. Targeting T. gondii PNP alone is unlikely to be efficacious for treatment of toxoplasmosis. 相似文献
994.
Non-ribosomal peptide synthetases (NRPSs) and polyketide synthases (PKSs) present in bacteria and fungi are the major multi-modular enzyme complexes which synthesize secondary metabolites like the pharmacologically important antibiotics and siderophores. Each of the multiple modules of an NRPS activates a different amino or aryl acid, followed by their condensation to synthesize a linear or cyclic natural product. The studies on NRPS domains, the knowledge of their gene cluster architecture and tailoring enzymes have helped in the in silico genetic screening of the ever-expanding sequenced microbial genomic data for the identification of novel NRPS/PKS clusters and thus deciphering novel non-ribosomal peptides (NRPs). Adenylation domain is an integral part of the NRPSs and is the substrate selecting unit for the final assembled NRP. In some cases, it also requires a small protein, the MbtH homolog, for its optimum activity. The presence of putative adenylation domain and MbtH homologs in a sequenced genome can help identify the novel secondary metabolite producers. The role of the adenylation domain in the NRPS gene clusters and its characterization as a tool for the discovery of novel cryptic NRPS gene clusters are discussed. 相似文献
995.
Pedalium murex (Pedaliaceae), commonly called Large Caltrops, is known for its pharmacological uses in traditional medicine system. It is reported to have excellent medicinal properties that helps cure reproductive disorders, mainly impotency in men, nocturnal emissions, gonorrhea as well as leucorrhoea in women. Apart from that, it also contains remedy for urinary and gastrointestinal tract disorders. Pharmacologically, the plant has been investigated for antiulcerogenic, nephroprotective, hypolipidemic, aphrodisiac, anti-inflammatory, antidermatophytic, antioxidant, antimicrobial and insecticidal activities. The present review is a bundle of information collected from the published research articles and highlights the phytochemical and pharmacological aspects of P. murex. The information will be helpful in developing the new formulation with therapeutic and economical value in the future. 相似文献
996.
997.
998.
Muhammad Imran Naseer Mahmood Rasool Osama Yousef Muthaffar Abdulrahman J. Sabbagh Adeel G. Chaudhary Mohammad H. Al-Qahtani 《Genes & genomics.》2017,39(12):1317-1323
Primary microcephaly (MCPH) is a rare developmental defect characterized by impaired cognitive functions, retarded neurodevelopment and reduced brain size. It is genetically heterogeneous and so far more than 17 genes associated with this disease have been identified. Primary microcephaly type 1 (MCPH1) gene encodes a protein called microcephalin, which is implicated in chromosome condensation and DNA damage induced cellular responses. It is suggested to play a role in neurogenesis and regulation of the size of the cerebral cortex. Whole exome sequencing revealed a novel, homozygous frameshift mutation (c.373_374delAA) in MCPH1 gene in exon 5 resulting in frameshift change from p.Lys125Glusfs*7. Our report presents the results of the simultaneous analysis of the trio exome data of both unaffected parents and their affected son. A homozygous frameshift variant in the MCPH1 gene was identified as a plausible candidate causal variant for the clinical phenotype in this family. 相似文献
999.
1000.
Physiological acclimation dampens initial effects of elevated temperature and atmospheric CO2 concentration in mature boreal Norway spruce
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Shubhangi Lamba Marianne Hall Mats Räntfors Nitin Chaudhary Sune Linder Danielle Way Johan Uddling Göran Wallin 《Plant, cell & environment》2018,41(2):300-313
Physiological processes of terrestrial plants regulate the land–atmosphere exchange of carbon, water, and energy, yet few studies have explored the acclimation responses of mature boreal conifer trees to climate change. Here we explored the acclimation responses of photosynthesis, respiration, and stomatal conductance to elevated temperature and/or CO2 concentration ([CO2]) in a 3‐year field experiment with mature boreal Norway spruce. We found that elevated [CO2] decreased photosynthetic carboxylation capacity (?23% at 25 °C) and increased shoot respiration (+64% at 15 °C), while warming had no significant effects. Shoot respiration, but not photosynthetic capacity, exhibited seasonal acclimation. Stomatal conductance at light saturation and a vapour pressure deficit of 1 kPa was unaffected by elevated [CO2] but significantly decreased (?27%) by warming, and the ratio of intercellular to ambient [CO2] was enhanced (+17%) by elevated [CO2] and decreased (?12%) by warming. Many of these responses differ from those typically observed in temperate tree species. Our results show that long‐term physiological acclimation dampens the initial stimulation of plant net carbon assimilation to elevated [CO2], and of plant water use to warming. Models that do not account for these responses may thus overestimate the impacts of climate change on future boreal vegetation–atmosphere interactions. 相似文献