342 research outputs found

    Ecology of Phlebotomine Sand Flies in the Rural Community of Mont Rolland (Thiès Region, Senegal): Area of Transmission of Canine Leishmaniasis

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    BACKGROUND: Different epidemiological studies previously indicated that canine leishmaniasis is present in the region of Thiès (Senegal). However, the risks to human health, the transmission cycle and particularly the implicated vectors are unknown. METHODOLOGY/PRINCIPAL FINDINGS: To improve our knowledge on the population of phlebotomine sand flies and the potential vectors of canine leishmaniasis, sand flies were collected using sticky traps, light traps and indoor spraying method using pyrethroid insecticides in 16 villages of the rural community of Mont Rolland (Thiès region) between March and July 2005. The 3788 phlebotomine sand flies we collected (2044 males, 1744 females) were distributed among 9 species of which 2 belonged to the genus Phlebotomus: P. duboscqi (vector of cutaneous leishmaniasis in Senegal) and P. rodhaini. The other species belonged to the genus Sergentomyia: S. adleri, S. clydei, S. antennata, S. buxtoni, S. dubia, S. schwetzi and S. magna. The number of individuals and the species composition differed according to the type of trap, suggesting variable, species-related degrees of endophily or exophily. The two species of the genus Phlebotomus were markedly under-represented in comparison to the species of the genus Sergentomyia. This study also shows a heterogeneous spatial distribution within the rural community that could be explained by the different ecosystems and particularly the soil characteristics of this community. Finally, the presence of the S. dubia species appeared to be significantly associated with canine leishmaniasis seroprevalence in dogs. CONCLUSIONS/SIGNIFICANCE: Our data allow us to hypothesize that the species of the genus Sergentomyia and particularly the species S. dubia and S. schwetzi might be capable of transmitting canine leishmaniasis. These results challenge the dogma that leishmaniasis is exclusively transmitted by species of the genus Phlebotomus in the Old World. This hypothesis should be more thoroughly evaluated

    Synthesis of γ-, δ-, and ε-Lactams by Asymmetric Transfer Hydrogenation of N-(tert-Butylsulfinyl)iminoesters

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    Highly enantiomerically enriched γ- and δ-lactams have been prepared by a simple and very efficient procedure that involves the asymmetric transfer hydrogenation of N-(tert-butylsulfinyl)iminoesters followed by desulfinylation of the nitrogen atom and spontaneous cyclization to the desired lactams during the basic workup procedure. Five- and six-membered ring lactams bearing aromatic, heteroaromatic, and aliphatic substituents have been obtained in very high yields and ee’s up to >99%. A slight modification of the procedure also allowed the preparation of ε-lactams in good yields and very high enantioselectivities. Both enantiomers of the final lactams could be prepared with equal efficiency by changing the absolute configuration of the sulfinyl chiral auxiliary

    Let’s not forget tautomers

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    A compound exhibits tautomerism if it can be represented by two structures that are related by an intramolecular movement of hydrogen from one atom to another. The different tautomers of a molecule usually have different molecular fingerprints, hydrophobicities and pKa’s as well as different 3D shape and electrostatic properties; additionally, proteins frequently preferentially bind a tautomer that is present in low abundance in water. As a result, the proper treatment of molecules that can tautomerize, ~25% of a database, is a challenge for every aspect of computer-aided molecular design. Library design that focuses on molecular similarity or diversity might inadvertently include similar molecules that happen to be encoded as different tautomers. Physical property measurements might not establish the properties of individual tautomers with the result that algorithms based on these measurements may be less accurate for molecules that can tautomerize—this problem influences the accuracy of filtering for library design and also traditional QSAR. Any 2D or 3D QSAR analysis must involve the decision of if or how to adjust the observed Ki or IC50 for the tautomerization equilibria. QSARs and recursive partitioning methods also involve the decision as to which tautomer(s) to use to calculate the molecular descriptors. Docking virtual screening must involve the decision as to which tautomers to include in the docking and how to account for tautomerization in the scoring. All of these decisions are more difficult because there is no extensive database of measured tautomeric ratios in both water and non-aqueous solvents and there is no consensus as to the best computational method to calculate tautomeric ratios in different environments
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