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71.
72.
Aranapakam M. Venkatesan Zecheng Chen Osvaldo Dos Santos Christoph Dehnhardt Efren Delos Santos Semiramis Ayral-Kaloustian Robert Mallon Irwin Hollander Larry Feldberg Judy Lucas Ker Yu Inder Chaudhary Tarek S. Mansour 《Bioorganic & medicinal chemistry letters》2010,20(19):5869-5873
A series of mono-morpholino 1,3,5-triazine derivatives (8a–8q) bearing a 3-oxa-8-azabicyclo[3.2.1]octane were prepared and evaluated for PI3-kinase/mTOR activity. Replacement of one of the bis-morpholines in lead compound 1 (PKI-587) with 3-oxa-8-azabicyclo[3.2.1]octane and reduction of the molecular weight yielded 8m (PKI-179), an orally efficacious dual PI3-kinase/mTOR inhibitor. The in vitro activity, in vivo efficacy, and PK properties of 8m are discussed. 相似文献
73.
Angel Casacó Irene Beausoleil Bárbara Gonzalez Patricia Luaces Avelina León María E. Arteaga Pavel Prado Valia Rodríguez Aylén Pérez Grisel Guevara Ana M. Bada Nuris Ledón Dasha Fuentes Consuelo González Osvaldo Hernandez Romy Orphee Diuris Blanco Miriam García‐Osuma Alcides Ballester‐Labrada 《Journal of medical primatology》2010,39(3):177-186
Background The purpose of this study is to better characterize the hematological, biochemical, respiratory, cardiovascular and electroneurophysiological parameters in young adult Cercopithecus aethiops sabaeus of both sexes. The rhesus and cynomolgus monkeys are widely used as experimental primate models. However, only few articles have been published testing toxicological effects of pharmaceuticals on African green monkey. Methods The present study was carried out with the recompilation of all parameters recorded before the first drug administration in five sub‐chronic or chronic toxicological studies performed on 66 Cercopithecus aethiops sabaeus, born in Cuba. Results This study provides hematological, biochemical, respiratory, cardiovascular and electroneurophysiological data for both choosing animals to be included into experiments and monitoring these parameters during the study. Conclusions We conclude that this study provides valuable integrated data for determining the health status, including electroneurophysiological parameters, data not previously reported for this species, of the African green monkey. 相似文献
74.
Luiz Henrique Saes Zobiole Edicléia Aparecida Bonini Rubem Silvério de OliveiraJr. Robert John Kremer Osvaldo Ferrarese-Filho 《Acta Physiologiae Plantarum》2010,32(5):831-837
Farmers report that some glyphosate-resistant soybean varieties are visually injured by glyphosate. Glyphosate is the main
herbicide that directly affects the synthesis of secondary compounds. In this work, we evaluated the effect of increasing
rates of glyphosate on lignin and amino acid content, photosynthetic parameters and dry biomass in the early maturity group
cultivar BRS 242 GR soybean. Plants were grown in half-strength complete nutrient solution and subjected to various rates
of glyphosate either as a single or in sequential applications. All parameters evaluated were affected by increasing glyphosate
rates. The effects were more pronounced as glyphosate rates increased, and were more intense with a single total application
than sequential applications at lower rates. 相似文献
75.
Derek V. Banthorpe Clifford A. Bunton Osvaldo Cori Martin J.O. Francis 《Phytochemistry》1985,24(2):251-252
Biosynthesis of several mono- and sesqui-terpenes that possess E or Z double bonds, or which are generally considered to be derived from precursors possessing such geometries, involved loss of the pro-4S hydrogen of mevalonate in the construction of the double bond. These results confirm and extend previous observations. A recent claim to have newly discovered such a stereochemical correlation is rejected. 相似文献
76.
Neem oil is a natural product obtained from the seeds of the tree Azadirachta indica. In this report, we investigate the alterations of the biophysical properties of the plasma membrane caused by treatment
with the nonterpenoid fraction of neem oil that we defined as methanolic extract (MEX). The dose-response effect was evaluated
and a MEX-dependent cytoxicity evidenced. The effect of MEX on the plasma membrane was studied by a well-established dielectric
spectroscopy technique: electrorotation, which allows single-cell analysis. Our results show a structural/functional alteration
of the plasma membrane with an evident increase of specific capacitance and conductance. The biological implications of this
effect are discussed. 相似文献
77.
Molecular dynamics simulations have been performed to investigate the interactions between chlorpromazine (CPZ) and Langmuir monolayers of the zwitterionic dipalmitoylphosphatidylcholine (DPPC) and the anionic dipalmitoylphosphatidylglycerol (DPPG). Simulations for a fixed surface density and different charge states - neutral and protonated CPZ - were able to capture important features of the CPZ-phospholipid monolayer interaction. Neutral CPZ is predominantly found in the hydrophobic tail region, whereas protonated CPZ is located at the lipid-water interface. Specific interactions (hydrogen bonds) between protonated CPZ and the lipid head groups were found for both zwitterionic and anionic monolayers. We computed lipid tail order parameters and investigated the effects of the drug upon tail ordering. We also computed electrostatic surface potentials and found qualitative good agreement with experimental results. 相似文献
78.
Matías García Azucena Gonzalez-Coloma Osvaldo J. Donadel Carlos E. Ardanaz Carlos E. Tonn Marta E. Sosa 《Biochemical Systematics and Ecology》2007
Flourensia oolepis Blake (Asteraceae) essential oil had a complex chemical composition with τ-muurolene (6.14%), santolinetriene (6.22%), 2-methylene-4,8,8-trimethyl-4-vinyl-bicyclo[5.2.0]nonane (10.15%), δ-cadinene (10.27%) and γ-gurjunene (20.69%) comprising more than 50% of the oil. This oil had repellent and toxic effects on Tribolium castaneum Herbst (Coleoptera: Tenebrionidae) adults, acting as a contact toxin. Myzus persicae (Sulzer) (Homoptera: Aphididae) and Leptinotarsa decemlineata Say (Coleoptera: Chrysomelidae) adults showed behavioral sensibility to this oil. 相似文献
79.
80.
Cherkasov A Hsing M Zoraghi R Foster LJ See RH Stoynov N Jiang J Kaur S Lian T Jackson L Gong H Swayze R Amandoron E Hormozdiari F Dao P Sahinalp C Santos-Filho O Axerio-Cilies P Byler K McMaster WR Brunham RC Finlay BB Reiner NE 《Journal of proteome research》2011,10(3):1139-1150
Mortality attributable to infection with methicillin-resistant Staphylococcus aureus (MRSA) has now overtaken the death rate for AIDS in the United States, and advances in research are urgently needed to address this challenge. We report the results of the systematic identification of protein-protein interactions for the hospital-acquired strain MRSA-252. Using a high-throughput pull-down strategy combined with quantitative proteomics to distinguish specific from nonspecific interactors, we identified 13,219 interactions involving 608 MRSA proteins. Consecutive analyses revealed that this protein interaction network (PIN) exhibits scale-free organization with the characteristic presence of highly connected hub proteins. When clinical and experimental antimicrobial targets were queried in the network, they were generally found to occupy peripheral positions in the PIN with relatively few interacting partners. In contrast, the hub proteins identified in this MRSA PIN that are essential for network integrity and stability have largely been overlooked as drug targets. Thus, this empirical MRSA-252 PIN provides a rich source for identifying critical proteins essential for network stability, many of which can be considered as prospective antimicrobial drug targets. 相似文献