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211.
Structure-activity relationships of tyrosinase inhibitory combinatorial library of 2,5-disubstituted-1,3,4-oxadiazole analogues 总被引:2,自引:0,他引:2
Khan MT Choudhary MI Khan KM Rani M Atta-ur-Rahman 《Bioorganic & medicinal chemistry》2005,13(10):3385-3395
Here the tyrosinase inhibition studies of library of 2,5-disubstituted-1,3,4-oxadiazoles have been reported and their structure-activity relationship (SAR) also have been discussed. The library of the oxadiazoles was synthesized under the microwave irradiation and was structures of these were characterized by different spectral techniques. From this study it could be concluded that for a better inhibition of tyrosinase, electronegative substitution is essential as most probably the active site of the enzyme contain some hydrophobic site and position is also very important for the inhibition purposes due to the conformational space. The electronegativity of the compounds is somewhat proportional to the inhibitory activity. The compound 3e (3'-[5-(4'-bromophenyl)-1,3,4-oxadiazol-2-yl]pyridine) exhibited most potent (IC50 = 2.18 microM) inhibition against the enzyme tyrosinase which is more potent than the standard potent inhibitor L-mimosine (IC50 = 3.68 microM). This molecule can be the best candidate as a lead compound for further development of drug for the treatments of several skin disorders. 相似文献
212.
Vascular endothelial growth factor (VEGF)-mediated angiogenesis is an important part of bone formation. To clarify the role of VEGF isoforms in endochondral bone formation, we examined long bone development in mice expressing exclusively the VEGF120 isoform (VEGF120/120 mice). Neonatal VEGF120/120 long bones showed a completely disturbed vascular pattern, concomitant with a 35% decrease in trabecular bone volume, reduced bone growth and a 34% enlargement of the hypertrophic chondrocyte zone of the growth plate. Surprisingly, embryonic hindlimbs at a stage preceding capillary invasion exhibited a delay in bone collar formation and hypertrophic cartilage calcification. Expression levels of marker genes of osteoblast and hypertrophic chondrocyte differentiation were significantly decreased in VEGF120/120 bones. Furthermore, inhibition of all VEGF isoforms in cultures of embryonic cartilaginous metatarsals, through the administration of a soluble receptor chimeric protein (mFlt-1/Fc), retarded the onset and progression of ossification, suggesting that osteoblast and/or hypertrophic chondrocyte development were impaired. The initial invasion by osteoclasts and endothelial cells into VEGF120/120 bones was retarded, associated with decreased expression of matrix metalloproteinase-9. Our findings indicate that expression of VEGF164 and/or VEGF188 is important for normal endochondral bone development, not only to mediate bone vascularization but also to allow normal differentiation of hypertrophic chondrocytes, osteoblasts, endothelial cells and osteoclasts. 相似文献
213.
Full-length archaeal Rad51 structure and mutants: mechanisms for RAD51 assembly and control by BRCA2 总被引:12,自引:0,他引:12 下载免费PDF全文
Shin DS Pellegrini L Daniels DS Yelent B Craig L Bates D Yu DS Shivji MK Hitomi C Arvai AS Volkmann N Tsuruta H Blundell TL Venkitaraman AR Tainer JA 《The EMBO journal》2003,22(17):4566-4576
To clarify RAD51 interactions controlling homologous recombination, we report here the crystal structure of the full-length RAD51 homolog from Pyrococcus furiosus. The structure reveals how RAD51 proteins assemble into inactive heptameric rings and active DNA-bound filaments matching three-dimensional electron microscopy reconstructions. A polymerization motif (RAD51-PM) tethers individual subunits together to form assemblies. Subunit interactions support an allosteric 'switch' promoting ATPase activity and DNA binding roles for the N-terminal domain helix-hairpin-helix (HhH) motif. Structural and mutational results characterize RAD51 interactions with the breast cancer susceptibility protein BRCA2 in higher eukaryotes. A designed P.furiosus RAD51 mutant binds BRC repeats and forms BRCA2-dependent nuclear foci in human cells in response to gamma-irradiation-induced DNA damage, similar to human RAD51. These results show that BRCA2 repeats mimic the RAD51-PM and imply analogous RAD51 interactions with RAD52 and RAD54. Both BRCA2 and RAD54 may act as antagonists and chaperones for RAD51 filament assembly by coupling RAD51 interface exchanges with DNA binding. Together, these structural and mutational results support an interface exchange hypothesis for coordinated protein interactions in homologous recombination. 相似文献
214.
Khan KM Maharvi GM Perveen S Khan MT Abdel-Jalil RJ Shah ST Fecker M Choudhary MI;Atta-ur-Rahman Voelter W 《化学与生物多样性》2005,2(4):470-476
The microwave-assisted synthesis and characterization of the ten new sildenafil (Viagra; 1) analogues 6-15 are described. A detailed structure-activity-relationship (SAR) study revealed that compounds 10 (= 4-ethoxy-N-hydroxy-3-(7-methoxy-1-methyl-3-propyl-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzenesulfonamide) and 12 (= S-(2-hydroxyethyl) 4-ethoxy-3-(7-methoxy-1-methyl-3-propyl-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzenesulfonothioate) are extremely potent mushroom tyrosinase inhibitors, with IC50 values (3.59 and 2.15 microM, resp.) below those of the standard inhibitors L-mimosine and kojic acid (IC50 = 3.68 and 16.67 microM, resp.). Compounds 10 and 12 are, thus, the currently most-effective inhibitors of tyrosinase, and bear great potential to be used for the treatment of various skin disorders such as hyperpigmentation, which is associated with high production of melanocytes. 相似文献
215.
216.
Margaret R. Dunne Louise Elliott Seamus Hussey Nasir Mahmud Jacinta Kelly Derek G. Doherty Conleth F. Feighery 《PloS one》2013,8(10)
Coeliac disease is a chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals. The only current therapy is a lifelong gluten free diet. While much work has focused on the gliadin-specific adaptive immune response in coeliac disease, little is understood about the involvement of the innate immune system. Here we used multi-colour flow cytometry to determine the number and frequency of γδ T cells (Vδ1, Vδ2 and Vδ3 subsets), natural killer cells, CD56+ T cells, invariant NKT cells, and mucosal associated invariant T cells, in blood and duodenum from adults and children with coeliac disease and healthy matched controls. All circulating innate lymphocyte populations were significantly decreased in adult, but not paediatric coeliac donors, when compared with healthy controls. Within the normal small intestine, we noted that Vδ3 cells were the most abundant γδ T cell type in the adult epithelium and lamina propria, and in the paediatric lamina propria. In contrast, patients with coeliac disease showed skewing toward a predominant Vδ1 profile, observed for both adult and paediatric coeliac disease cohorts, particularly within the gut epithelium. This was concurrent with decreases in all other gut lymphocyte subsets, suggesting a specific involvement of Vδ1 cells in coeliac disease pathogenesis. Further analysis showed that γδ T cells isolated from the coeliac gut display an activated, effector memory phenotype, and retain the ability to rapidly respond to in vitro stimulation. A profound loss of CD56 expression in all lymphocyte populations was noted in the coeliac gut. These findings demonstrate a sustained aberrant innate lymphocyte profile in coeliac disease patients of all ages, persisting even after elimination of gluten from the diet. This may lead to impaired immunity, and could potentially account for the increased incidence of autoimmune co-morbidity. 相似文献
217.
Habitat Characteristics of the Endangered Hoolock Gibbons of Bangladesh: The Role of Plant Species Richness 总被引:1,自引:0,他引:1
Sabir Bin Muzaffar M. Anwarul Islam Mostafa M. Feeroz Mofizul Kabir Sajeda Begum M. Shahriar Mahmud Suprio Chakma M. Kamrul Hasan 《Biotropica》2007,39(4):539-545
Hoolock gibbons ( Hoolock hoolock ) are endangered small apes occurring in Bangladesh, India, Myanmar, and south China. All known populations have undergone declines primarily due to habitat destruction or alteration. We examined the influence of area of natural forests, area of plantations, area of agricultural land and edible plant species richness on the hoolock gibbon numbers from 22 sites in Bangladesh using multiple regression analysis. Area of natural forests and plantations were not linked to hoolock gibbon numbers, whereas area of agricultural land and edible plant species richness were both significantly linked. Higher edible plant species richness was directly related to hoolock gibbon numbers, while the area of agricultural land was inversely related. This is the first quantitative study illustrating the importance of these two variables with hoolock gibbon numbers. We also analyzed the existing habitat characteristics in two of the largest hoolock gibbon populations in Bangladesh: Lawachara (42 individuals) and Kaptai (84 individuals). Trees in Lawachara were generally smaller compared to those in Kaptai. Artocarpus , Tectona , and Dipterocarpus were the three most important genera in both sites, although Artocarpus was more important in Lawachara. Each site also had an abundant variety of tree species utilized by hoolock gibbons for food. We discuss the current context of primate conservation in Bangladesh and suggest that the current conservation priority for gibbons in the country should be protection and improvement of habitat. 相似文献
218.
Abdul Awal Chowdhury Masud Md. Fazlul Karim M. H. M. Borhannuddin Bhuyan Jubayer Al Mahmud Kamrun Nahar Masayuki Fujita Mirza Hasanuzzaman 《Phyton》2021,90(2):353-372
Drought is the most common form of abiotic stress that reduces plant growth and productivity. It causes plant
injuries through elevated production of reactive oxygen species (ROS). Potassium (K) is a vital plant nutrient that
notably ameliorates the detrimental effect of drought stress in the plant. A pot experiment was conducted at the
Laboratory of Plant Stress Responses, Faculty of Agriculture, Kagawa University, Japan, under controlled environment of green house to explore the role of K in mitigating drought severity in wheat (Triticum asevitum L.)
seedlings. Three days after germination, seedlings were exposed to three water regimes viz., 100, 50, and 20% field
capacity (FC) for 21 days. Potassium was adjusted in Hoagland nutrient solution at 0, 6 and 12 mM concentration
and applied to pot instead of normal water. Results show that, water deficit stress notably reduced plant growth,
biomass accumulation, leaf relative water content (RWC) along with reduced photosynthetic pigments. Increased
amount of biochemical stress markers viz., malondialdehyde (MDA), hydrogen peroxide (H2O2), methylglyoxal
(MG), proline (Pro) as well as an impaired antioxidant defense system were observed in drought affected wheat
plants. On the contrary, K supplementation resulted in improvement of biochemical and physiological parameters
that worked behind in improving growth and development of the wheat plants. In addition, enzymes of ascorbateglutathione (AsA-GSH) cycle were also enhanced by supplemented K that accelerated the ROS detoxification process in plant. Although glyoxalse system did not performed well till MG was detoxified might following another
short stepped pathways. Our results revealed that drought stressed plants showed better performances in terms of
biochemical and physiological attributes, antioxidant defense and glyoxalase system, as well as ROS detoxification
due to K supplementation with better performance at 12 mM K added in 50% FC growing condition. 相似文献
219.
Ahmed K. Al-Delaimy Hesham M. Al-Mekhlafi Nabil A. Nasr Hany Sady Wahib M. Atroosh Mohammed Nashiry Tengku S. Anuar Norhayati Moktar Yvonne A. L. Lim Rohela Mahmud 《PLoS neglected tropical diseases》2014,8(8)
Background
This cross-sectional study aimed to investigate the current prevalence and risk factors associated with intestinal polyparasitism (the concurrent infection with multiple intestinal parasite species) among Orang Asli school children in the Lipis district of Pahang state, Malaysia.Methods/Principal findings
Fecal samples were collected from 498 school children (50.6% boys and 49.4% girls), and examined by using direct smear, formalin-ether sedimentation, trichrome stain, modified Ziehl Neelsen stain, Kato-Katz, and Harada Mori techniques. Demographic, socioeconomic, environmental, and personal hygiene information were collected by using a pre-tested questionnaire. Overall, 98.4% of the children were found to be infected by at least one parasite species. Of these, 71.4% had polyparasitism. The overall prevalence of Trichuris trichiura, Ascaris lumbricoides, hookworm, Giardia duodenalis, Entamoeba spp., and Cryptosporidium spp. infections were 95.6%, 47.8%, 28.3%, 28.3%, 14.1% and 5.2%, respectively. Univariate and multivariate analyses showed that using an unsafe water supply as a source for drinking water, presence of other family members infected with intestinal parasitic infections (IPI), not washing vegetables before consumption, absence of a toilet in the house, not wearing shoes when outside, not cutting nails periodically, and not washing hands before eating were significant risk factors associated with intestinal polyparasitism among these children.Conclusions/Significance
Intestinal polyparasitism is highly prevalent among children in the peninsular Malaysian Aboriginal communities. Hence, effective and sustainable control measures, including school-based periodic chemotherapy, providing adequate health education focused on good personal hygiene practices and proper sanitation, as well as safe drinking water supply should be implemented to reduce the prevalence and consequences of these infections in this population. 相似文献220.
Allison L. Creason Olivier M. Vandeputte Elizabeth A. Savory Edward W. Davis II Melodie L. Putnam Erdong Hu David Swader-Hines Adeline Mol Marie Baucher Els Prinsen Magdalena Zdanowska Scott A. Givan Mondher El Jaziri Joyce E. Loper Taifo Mahmud Jeff H. Chang 《PloS one》2014,9(7)
Members of Gram-positive Actinobacteria cause economically important diseases to plants. Within the Rhodococcus genus, some members can cause growth deformities and persist as pathogens on a wide range of host plants. The current model predicts that phytopathogenic isolates require a cluster of three loci present on a linear plasmid, with the fas operon central to virulence. The Fas proteins synthesize, modify, and activate a mixture of growth regulating cytokinins, which cause a hormonal imbalance in plants, resulting in abnormal growth. We sequenced and compared the genomes of 20 isolates of Rhodococcus to gain insights into the mechanisms and evolution of virulence in these bacteria. Horizontal gene transfer was identified as critical but limited in the scale of virulence evolution, as few loci are conserved and exclusive to phytopathogenic isolates. Although the fas operon is present in most phytopathogenic isolates, it is absent from phytopathogenic isolate A21d2. Instead, this isolate has a horizontally acquired gene chimera that encodes a novel fusion protein with isopentyltransferase and phosphoribohydrolase domains, predicted to be capable of catalyzing and activating cytokinins, respectively. Cytokinin profiling of the archetypal D188 isolate revealed only one activate cytokinin type that was specifically synthesized in a fas-dependent manner. These results suggest that only the isopentenyladenine cytokinin type is synthesized and necessary for Rhodococcus phytopathogenicity, which is not consistent with the extant model stating that a mixture of cytokinins is necessary for Rhodococcus to cause leafy gall symptoms. In all, data indicate that only four horizontally acquired functions are sufficient to confer the trait of phytopathogenicity to members of the genetically diverse clade of Rhodococcus. 相似文献