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91.
Vijeta Sharma Nagarjuna Amarnath Swapnil Shukla R. Ayana Naveen Kumar Nisha Yadav Deepika Kannan Seema Sehrawat Soumya Pati Bimlesh Lochab Shailja Singh 《Bioorganic & medicinal chemistry letters》2018,28(9):1629-1637
Development of new class of anti-malarial drugs is an essential requirement for the elimination of malaria. Bioactive components present in medicinal plants and their chemically modified derivatives could be a way forward towards the discovery of effective anti-malarial drugs. Herein, we describe a new class of compounds, 1,3-benzoxazine derivatives of pharmacologically active phytophenols eugenol (compound 3) and isoeugenol (compound 4) synthesised on the principles of green chemistry, as anti-malarials. Compound 4, showed highest anti-malarial activity with no cytotoxicity towards mammalian cells. Compound 4 induced alterations in the intracellular Na+ levels and mitochondrial depolarisation in intraerythrocytic Plasmodium falciparum leading to cell death. Knowing P-type cation ATPase PfATP4 is a regulator for sodium homeostasis, binding of compound 3, compound 4 and eugenol to PfATP4 was analysed by molecular docking studies. Compounds showed binding to the catalytic pocket of PfATP4, however compound 4 showed stronger binding due to the presence of propylene functionality, which corroborates its higher anti-malarial activity. Furthermore, anti-malarial half maximal effective concentration of compound 4 was reduced to 490?nM from 17.54?µM with nanomaterial graphene oxide. Altogether, this study presents anti-plasmodial potential of benzoxazine derivatives of phytophenols and establishes disruption of parasite sodium homeostasis as their mechanism of action. 相似文献
92.
Sam Nirmala Nisha Gajjeraman Prabu Abul Kalam Azad Mandal 《Physiology and Molecular Biology of Plants》2018,24(5):867-880
Tea (Camellia sinensis) plantations are exposed to biotic and abiotic stresses. Among the biotic factors, blister blight (BB), caused by Exobasidium vexans, affects the quality and quantity of the product and demands high fungicide application. A long term solution for disease resistance would require the knowledge of the basic molecular and biochemical changes occurring in plant as an attempt to resist the pathogen and limit the spread of the disease which can further help in developing resistant cultivars using biotechnological tools. Thus, gene expression studies using the cDNA based suppressive subtractive hybridization library, characterization of genes for pathogenesis related (PR) proteins [chitinase (CsCHIT), glucanase (CsGLUC), phenylalanine ammonia lyase (CsPAL)] and genes in flavonoid pathway were accessed in the BB resistant and susceptible cultivars, SA6 and TES34, respectively. Further, biochemical analysis of PR and antioxidant enzymes (POX, APX, SOD) involved in BB resistance have been carried out to investigate the potential molecular and biochemical changes. Various stages of pathogen development had varied impact on PR protein, flavonoid pathway and anti-oxidative enzymes and indicates the possible role of reactive oxygen species, lignins, flavonoids, anthocyanins and other synthesized compounds in acting as antimicrobial/antifungal agents in tea cultivars. 相似文献
93.
Sven Ruf Mahanandeesha Siddappa Hallur Nisha K. Anchan Indu N. Swamy Karthikai Raj Murugesan Sayantani Sarkar Lokesh Kananti Narasimhulu V.P. Rama Kishore Putta Shama Shaik Devaraj Venkatapura Chandrasekar Vishal Subhash Mane Sanjay Venkatachalapathi Kadnur Juluri Suresh Ravi Kanth Bhamidipati Manvi Singh Raghunadha Reddy Burri Rajendra Kristam Herman Schreuder Sridharan Rajagopal 《Bioorganic & medicinal chemistry letters》2018,28(5):922-925
Nicotinamide N-methyltransferase (NNMT) has been linked to obesity and diabetes. We have identified a novel nicotinamide (NA) analog, compound 12 that inhibited NNMT enzymatic activity and reduced the formation of 1-methyl-nicotinamide (MNA), the primary metabolite of NA by ~80% at 2?h when dosed in mice orally at 50?mg/kg. 相似文献
94.
Shoot regeneration has been achieved in Zizyphus mauritiana from juvenile explants (internodal and nodal segments) on MS medium containing 2% sucrose and 50 mg l?1 each of asparagine, arginine and glutamine, 5 mg l?1 cystelne hydrochloride and various combinations of IAA/zeatin, BAP, KN and Ad. The explants were most responsive on the medium containing zeatin followed by BAP. Callusing could be induced from all parts of the seedling viz. cotyledonary leaf, hypocotyl, epicotyl, leaf and nodal region on various media tried. Expression of peroxidase and esterase in the in vivo and in vitro grown tissues was also compared through starch gel electrophoresis. 相似文献
95.
BackgroundThe anti–human epidermal growth factor receptor 2 (HER2) monoclonal antibody trastuzumab improves outcomes in patients with node-positive HER2+ early breast cancer. Given trastuzumab’s high cost, we aimed to estimate its cost-effectiveness by heterogeneity in age and estrogen receptor (ER) and progesterone receptor (PR) status, which has previously been unexplored, to assist prioritisation.ConclusionsThis study highlights how cost-effectiveness can vary greatly by heterogeneity in age and hormone receptor subtype. Resource allocation and licensing of subsidised therapies such as trastuzumab should consider demographic and clinical heterogeneity; there is currently a profound disconnect between how funding decisions are made (largely agnostic to heterogeneity) and the principles of personalised medicine. 相似文献
96.
ABSTRACTIn the spirit of ‘furthering debate and reflection’ in this response to Theories of Race and Ethnicity, we consider here the pertinence of the theme of resistance that occupies particular chapters within the collection and that has been central to key works within the wider race critical scholarship. Yet, when the larger field of contemporary race study is considered, we also note that other contiguous concerns – including capitalism, religion, nation, and war – are key factors in thinking through racism. Here, we further elaborate on how future theorizations of race and ethnicity must engage with these domains. 相似文献
97.
98.
Introduction
Low and middle income countries bear the majority burden of self-harm, yet there is a paucity of evidence detailing risk-factors for self-harm in these populations. This study aims to identify environmental, socio-economic and demographic household-level risk factors for self-harm in five impoverished urban communities in Johannesburg, South Africa.Methods
Annual serial cross-sectional surveys were undertaken in five impoverished urban communities in Johannesburg for the Health, Environment and Development (HEAD) study. Logistic regression analysis using the HEAD study data (2006–2011) was conducted to identify household-level risk factors associated with self-harm (defined as a self-reported case of a fatal or non-fatal suicide attempt) within the household during the preceding year. Stepwise multivariate logistic regression analysis was employed to identify factors associated with self-harm.Results
A total of 2 795 household interviews were conducted from 2006 to 2011. There was no significant trend in self-harm over time. Results from the final model showed that self-harm was significantly associated with households exposed to a violent crime during the past year (Adjusted Odds Ratio (AOR) 5.72; 95% CI 1.64–19.97); that have a member suffering from a chronic medical condition (AOR 8.95; 95% 2.39–33.56) and households exposed to indoor smoking (AOR 4.39; CI 95% 1.14–16.47).Conclusion
This study provides evidence on household risk factors of self-harm in settings of urban poverty and has highlighted the potential for a more cost-effective approach to identifying those at risk of self-harm based on household level factors. 相似文献99.
K. Sreevishnupriya P. Chandrasekaran A. Senthilkumar R. Sethumadhavan V. Shanthi P. Daisy J. Nisha K. Ramanathan R. Rajasekaran 《中国科学:生命科学英文版》2012,55(12):1109-1119
In this work, the most detrimental missense mutations of aspartoacylase that cause Canavan??s disease were identified computationally and the substrate binding efficiencies of those missense mutations were analyzed. Out of 30 missense mutations, I-Mutant 2.0, SIFT and PolyPhen programs identified 22 variants that were less stable, deleterious and damaging respectively. Subsequently, modeling of these 22 variants was performed to understand the change in their conformations with respect to the native aspartoacylase by computing their root mean squared deviation (RMSD). Furthermore, the native protein and the 22 mutants were docked with the substrate NAA (N-Acetyl-Aspartic acid) to explain the substrate binding efficiencies of those detrimental missense mutations. Among the 22 mutants, the docking studies identified that 15 mutants caused lower binding affinity for NAA than the native protein. Finally, normal mode analysis determined that the loss of binding affinity of these 15 mutants was caused by altered flexibility in the amino acids that bind to NAA compared with the native protein. Thus, the present study showed that the majority of the substrate-binding amino acids in those 15 mutants displayed loss of flexibility, which could be the theoretical explanation of decreased binding affinity between the mutant aspartoacylases and NAA. 相似文献
100.
Functional interrelation of MYC2 and HY5 plays an important role in Arabidopsis seedling development