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81.
Thompson MJ Louth JC Little SM Jackson MP Boursereau Y Chen B Coldham I 《ChemMedChem》2012,7(4):578-586
Malaria is one of the world's most devastating parasitic diseases, causing almost one million deaths each year. Growing resistance to classical antimalarial drugs, such as chloroquine, necessitates the discovery of new therapeutic agents for successful control of this global disease. Here, we report the synthesis of some 6-halo-β-carbolines as analogues of the potent antimalarial natural product, manzamine A, retaining its heteroaromatic core whilst providing compounds with much improved synthetic accessibility. Two compounds displayed superior activity to chloroquine itself against a resistant Plasmodium falciparum strain, identifying them as promising leads for future development. Furthermore, in line with previous reports of similarities in antimalarial and antiprion effects of aminoaryl-based antimalarial agents, the 1-amino-β-carboline libraries were also found to possess significant bioactivity against a prion-infected cell line. 相似文献
82.
In this paper, a new nanostructure is proposed, namely, the knitted graphene-nanoribbon sheet (KGS), which consists of zigzag and/or armchair graphene nanoribbons. The knitting technology is introduced to graphene nanotechnology to produce large area graphene sheets. Compared with pristine graphene, the chirality of a knitted graphene-nanoribbon sheet is much more flexible and can be designed on demand. The mechanical properties of KGSs are investigated by molecular dynamics simulations, including the effect of vacancies. With hydrogen atoms saturating the ribbon edges, the structure (KGS + H) is found to be of significant mechanical robustness, whose fracture does not rely on the critical bonds. The fracture strain of KGS + H remains nearly unchanged as long as there remains a single defect-free graphene nanoribbon in the tensile direction. This graphene nano knitting technique is experimentally feasible, inspired by a recent demonstration by Fournier et al. [Phys. Rev. B, 2011, 84, 035435] of lifting a single molecular wire using a combined frequency-modulated atomic force and tunnelling microscope. 相似文献
83.
84.
Dietary fat and body weight control 总被引:3,自引:0,他引:3
The global obesity epidemic has heightened the debate about dietary factors contributing to weight gain. Media stories have
promulgated the notion that obesity has increased despite reductions in dietary fat intake. Some have even speculated that
lower dietary fat levels may be driving the rapid rise in weight gain within the population. A close examination of the science
reveals a different picture and supports the hypothesis that dietary fat, within the context of the total dietary composition
consumed by many populations, promotes obesity. Hence, dietary fat control is still an important strategy as part of an overall
approach to body weight management in our modern environment. Dietary fat increases the energy density of foods. Abundant
evidence from preclinical and clinical studies indicates that fat promotes excess energy intake and positive energy balance.
Dietary fat does not promote its own oxidation in the body and is stored efficiently, promoting a positive fat balance. Thus,
both the behavioral and metabolic responses to dietary fat increase the probability of positive energy balance and body fat
gain. Restoring fat balance when consuming diets rich in fat requires increasing the size of the body fat mass, increasing
physical activity, or reducing dietary fat intake. Numerous epidemiologic, preclinical, and controlled clinical studies have
shown that body fat is positively associated with dietary fat intake and that dietary fat manipulation leads to appropriate
changes in body fat mass. Finally, data from the National Weight Control Registry, a database of >3000 individuals who have
successfully maintained a substantial weight loss, indicate that moderating dietary fat intake is a key strategy for long-term
management of body weight. 相似文献
85.
The booklouse, Liposcelis bostrychophila, is an increasingly common pest of stored food products worldwide. We report here the cuticular lipid composition of this pest (the first report of the hydrocarbons of any member of the Order Psocoptera and the first report of fatty acid amides as cuticular components for any insect). No unsaturated hydrocarbons were present. A homologous series of n-alkanes (C21–C34), monomethyl alkanes (3-, 4-, 5-, 7-, 9-, 11-, 12-, 13- and 15-methyl-) with a carbon chain range of C28–C42, and dimethyl alkanes (3, 7-; 9, 13-; 11, 15-; 13, 17-; 9, 21-; 11, 19-; and 13, 21-); with a carbon number range of C31–C43 were identified. The relative abundances of these hydrocarbons were low, comprising approximately 0.0125% of total biomass. The amides were a homologous series (C16–C22 in chain length), with the major amide being stearoyl amide. In addition to the amides, free fatty acids (C16:1, C16:0, C18:2, C18:1, and C18:0 in chain length) and three straight chain aldehydes (C15, C16, and C17:1 in chain length) also occurred as cuticular components. These findings are discussed in terms of the chemical and physiological ecology of this species. 相似文献
86.
The attractiveness of different synthetic host odors and a synthetic aggregation pheromone (grandisoic acid [GA]) to overwintered adult plum curculios (PCs), Conotrachelus nenuphar (Herbst) (Coleoptera: Curculionidae), was examined using two types of traps (sticky panels and black pyramids) placed in border areas surrounding an unsprayed section of an apple orchard in Massachusetts. In 2001, we evaluated the response of PCs to three synthetic fruit volatiles (benzaldehyde [BEN], ethyl isovalerate [EIV], and limonene [LIM]) assessed alone and in combination with GA, as well as the response to GA alone and a no-odor (control) treatment. BEN was the only host volatile that synergized the response of PCs to GA for both trap types. For both trap types, GA was as attractive to PCs as a single component as when in combination with either EIV or LIM. In 2002, four release rates of BEN (0, 2.5, 10, and 40 mg/day) and two release rates of GA (1 and 2 mg/day) were evaluated for attractiveness to PCs using panel and pyramid traps. For panel traps, an increase in amount of GA released (from 1 to 2 mg/day) was associated with a 35% increase in captures. However, PC captures by pyramid traps were similar regardless of the amount of GA released. For panel traps, 10 and 40 mg/day of BEN were the most attractive release rates regardless of the amount of GA released. For pyramid traps baited with GA. PC captures were enhanced by the presence of BEN, regardless of release rate. In 2003, GA at 1 mg/day + BEN at 80 mg/day of release did not enhance PC captures by panel traps relative to lower release rates of BEN. Pyramid traps releasing GA at 1 mg/day performed best when baited with BEN at 10 mg/day of release; a release rate of 80 mg/day of BEN decreased the attractiveness of the binary combination of BEN + GA. Combined results suggest that BEN at 10 mg/day + GA at 1 mg/day of release constitutes an attractive lure that may improve the effectiveness of monitoring traps for PCs. 相似文献
87.
Salmain M Caro B Le Guen-Robin F Blais JC Jaouen G 《Chembiochem : a European journal of chemical biology》2004,5(1):99-109
Study of the reaction between the transition organometallic complex 4-ruthenocenyl 2,6-dimethylpyrylium tetrafluoroborate and the enzyme hen egg white lysozyme (HEWL) in solution and by diffusion in crystals was performed by use of a combination of spectroscopic and chromatographic methods. Conjugation involving the lysine residues of lysozyme appeared to occur readily, yielding very stable ruthenocenyl pyridinium adducts with average degrees of incorporation ranging from 0.2 to 1.8 metal complexes per protein molecule, depending on reaction conditions. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) revealed that the protein conjugates were in fact mixtures of unmodified, mono-, di- and sometimes tripyridinium adducts. In combination with reversed-phased HPLC, we were able to show that six different monoruthenocenyl pyridinium adducts were formed in solution. This result was confirmed by trypsin digestion of a ruthenocenyl pyridinium conjugate and MALDI-TOF MS analysis of the peptide mixture, which showed that lysines 1, 13, 33, 96, 97 and 116 were involved in the reaction with the pyrylium complex, lysines 13, 33 and 116 being the major binding sites. In the tetragonal crystal state, no binding of the ruthenium complex was shown to occur at lysine 116, owing to steric hindrance at this particular position. 相似文献
88.
Figueroa CC Simon JC Le Gallic JF Prunier-Leterme N Briones LM Dedryver CA Niemeyer HM 《Journal of chemical ecology》2004,30(12):2515-2525
Five microsatellite loci were used to study the genetic variability and population structure of Sitobion avenae (Hemiptera: Aphididae) on some of its host plants. Individuals were collected in Chile from different cultivated and wild Poaceae. Forty-four multilocus genotypes were found among the 1052 aphids analyzed, of which four represented nearly 90% of the sample. No specialist genotypes were found, although some preferred hosts endowed with chemical defenses, i.e., hydroxamic acids (Hx), while others preferred comparatively undefended hosts. Performances of some predominant and some rare genotypes were evaluated on plants differing in their Hx levels. Significant differences in performance were found among clones, the two most common genotypes showing no differences in performance among all hosts tested, and the rare genotypes showing enhanced performance on the host with highest Hx level. A hypothesis is proposed whereby the appearance of rarer genotypes is in part related to the presence of Hx. 相似文献
89.
We identified and quantified the hydroperoxides, hydroxides, epoxides, isoprostanes, and core aldehydes of the major phospholipids
as the main components of the oxophospholipids (a total of 5–25 pmol/μmol phosphatidylcholine) in a comparative study of human
atheroma from selected stages of lesion development. The developmental stages examined included fatty streak, fibrous plaque,
necrotic core, and calcified tissue. The lipid analyses were performed by normal-phase HPLC with on-line electrospray MS using
conventional total lipid extracts. There was great variability in the proportions of the various oxidation products and a
lack of a general trend. Specifically, the early oxidation products (hydroperoxides and epoxides) of the glycerophosphocholines
were found at the advanced stages of the plaques in nearly the same relative abundance as the more advanced oxidation products
(core aldehydes and acids). The anticipated linear accumulation of the more stable oxidation products with progressive development
of the atherosclerotic plaque was not apparent. It is therefore suggested that lipid infiltration and/or local peroxidation
is a continuous process characterized by the formation and destruction of both early and advanced products of lipid oxidation
at all times. The process of lipid deposition appears to have been subject to both enzymatic and chemical modification of
the normal tissue lipids. Clearly, the appearance of new and disproportionate old lipid species excludes randomness in any
accumulation of oxidized LDL lipids in atheroma. 相似文献
90.
Mach UR Hackling AE Perachon S Ferry S Wermuth CG Schwartz JC Sokoloff P Stark H 《Chembiochem : a European journal of chemical biology》2004,5(4):508-518
Based on N-alkylated 1,2,3,4-tetrahydroisoquinoline derivatives, which are structurally related to the partial agonist BP 897, a series of novel, selective dopamine D3 receptor antagonists has been synthesised. Derivatisation included changes in the arylamide moiety and the tetrahydroisoquinoline substructure leading to compounds with markedly improved selectivities and affinities in the low nanomolar concentration range. From the 55 structures presented here, (E)-3-(4-iodophenyl)-N-(4-(1,2,3,4-tetrahydroisoquinolin-2-yl)butyl)acrylamide (51) has high affinity (Ki(hD3)=12 nM) and a 123-fold preference for the D3 receptor relative to the D2 receptor subtype. Its pharmacological profile offers the prospect of a novel radioligand as a tool for various dopamine D3-receptor-related in vitro and in vivo investigations. 相似文献